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MicroRNA (miRNA) circulating in plasma have been proposed as biomarkers for a variety of conditions and diseases, including complications during pregnancy. During pregnancy, about 15–25% of maternal plasma exosomes, a small size-class of EVs, are hypothesized to originate in the placenta, and may play a role in communication between the fetus and mother. However, few studies have addressed changes in miRNA over the course of pregnancy with repeated measures, nor focused on diverse populations. We describe changes in miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, CA. miRNA derived from extracellular-vesicles (EVs) were isolated from maternal blood plasma samples collected in early and late pregnancy. In this study, we identified 64 of 130 detectable miRNA which significantly increased with gestational age at the time of collection (GA), and 26 which decreased with GA. Possible fetal sex-specific associations were observed for 30 of these 90 significant miRNA. Predicted gene targets for miRNA significantly associated with GA were identified using MirDIP and were found to be enriched for Gene Ontology categories that included energetic and metabolic processes but were underrepresented in immune-related categories. Circulating EV-associated miRNA during pregnancy are likely important for maternal-fetal communication, and may play roles in supporting and maintaining a healthy pregnancy, given the changing needs of the fetus.
Helen Bermudez Foley; Caitlin G. Howe; Sandrah P. Eckel; Thomas Chavez; Lili Gevorkian; Eileen Granada Reyes; Bethany Kapanke; Danilo Martinez; Shanyan Xue; Shakira F. Suglia; Theresa M. Bastain; Carmen Marsit; Carrie V. Breton. Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort. PLOS ONE 2021, 16, e0251259 .
AMA StyleHelen Bermudez Foley, Caitlin G. Howe, Sandrah P. Eckel, Thomas Chavez, Lili Gevorkian, Eileen Granada Reyes, Bethany Kapanke, Danilo Martinez, Shanyan Xue, Shakira F. Suglia, Theresa M. Bastain, Carmen Marsit, Carrie V. Breton. Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort. PLOS ONE. 2021; 16 (5):e0251259.
Chicago/Turabian StyleHelen Bermudez Foley; Caitlin G. Howe; Sandrah P. Eckel; Thomas Chavez; Lili Gevorkian; Eileen Granada Reyes; Bethany Kapanke; Danilo Martinez; Shanyan Xue; Shakira F. Suglia; Theresa M. Bastain; Carmen Marsit; Carrie V. Breton. 2021. "Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort." PLOS ONE 16, no. 5: e0251259.
Circulating miRNA may contribute to the development of adverse birth outcomes. However, few studies have investigated extracellular vesicle (EV) miRNA, which play important roles in intercellular communication, or compared miRNA at multiple time points in pregnancy. In the current study, 800 miRNA were profiled for EVs from maternal plasma collected in early (median: 12.5 weeks) and late (median: 31.8 weeks) pregnancy from 156 participants in the MADRES Study, a health disparity pregnancy cohort. Associations between miRNA and birth weight, birth weight for gestational age (GA), and GA at birth were examined using covariate-adjusted robust linear regression. Differences by infant sex and maternal BMI were also investigated. Late pregnancy measures of 13 miRNA were associated with GA at birth (PFDR<0.050). Negative associations were observed for eight miRNA (miR-4454+ miR-7975, miR-4516, let-7b-5p, miR-126-3p, miR-29b-3p, miR-15a-5p, miR-15b-5p, miR-19b-3p) and positive associations for five miRNA (miR-212-3p, miR-584-5p, miR-608, miR-210-3p, miR-188-5p). Predicted target genes were enriched (PFDR<0.050) in pathways involved in organogenesis and placental development. An additional miRNA (miR-107), measured in late pregnancy, was positively associated with GA at birth in infants born to obese women (PFDR for BMI interaction = 0.011). In primary analyses, the associations between early pregnancy miRNA and birth outcomes were not statistically significant (PFDR≥0.05). However, sex-specific associations were observed for early pregnancy measures of 37 miRNA and GA at birth (PFDR for interactions<0.050). None of the miRNA were associated with fetal growth measures (PFDR≥0.050). Our findings suggest that EV miRNA in both early and late pregnancy may influence gestational duration.
Caitlin G Howe; Helen B Foley; Elizabeth M Kennedy; Sandrah P Eckel; Thomas a Chavez; Dema Faham; Brendan H Grubbs; Laila Al-Marayati; Deborah Lerner; Shakira Suglia; Theresa M Bastain; Carmen J Marsit; Carrie V Breton. Extracellular vesicle microRNA in early versus late pregnancy with birth outcomes in the MADRES study. Epigenetics 2021, 1 -17.
AMA StyleCaitlin G Howe, Helen B Foley, Elizabeth M Kennedy, Sandrah P Eckel, Thomas a Chavez, Dema Faham, Brendan H Grubbs, Laila Al-Marayati, Deborah Lerner, Shakira Suglia, Theresa M Bastain, Carmen J Marsit, Carrie V Breton. Extracellular vesicle microRNA in early versus late pregnancy with birth outcomes in the MADRES study. Epigenetics. 2021; ():1-17.
Chicago/Turabian StyleCaitlin G Howe; Helen B Foley; Elizabeth M Kennedy; Sandrah P Eckel; Thomas a Chavez; Dema Faham; Brendan H Grubbs; Laila Al-Marayati; Deborah Lerner; Shakira Suglia; Theresa M Bastain; Carmen J Marsit; Carrie V Breton. 2021. "Extracellular vesicle microRNA in early versus late pregnancy with birth outcomes in the MADRES study." Epigenetics , no. : 1-17.
Background Child blood pressure (BP) is predictive of future cardiovascular risk. Prenatal exposure to metals has been associated with higher BP in childhood, but most studies have evaluated elements individually and measured BP at a single time point. We investigated impacts of prenatal metal mixture exposures on longitudinal changes in BP during childhood and elevated BP at 11 years of age. Methods The current study included 176 mother-child pairs from the Rhea Study in Heraklion, Greece and focused on eight elements (antimony, arsenic, cadmium, cobalt, lead, magnesium, molybdenum, selenium) measured in maternal urine samples collected during pregnancy (median gestational age at collection: 12 weeks). BP was measured at approximately 4, 6, and 11 years of age. Covariate-adjusted Bayesian Varying Coefficient Kernel Machine Regression and Bayesian Kernel Machine Regression (BKMR) were used to evaluate metal mixture impacts on baseline and longitudinal changes in BP (from ages 4 to 11) and the development of elevated BP at age 11, respectively. BKMR results were compared using static versus percentile-based cutoffs to define elevated BP. Results Molybdenum and lead were the mixture components most consistently associated with BP. J-shaped relationships were observed between molybdenum and both systolic and diastolic BP at age 4. Similar associations were identified for both molybdenum and lead in relation to elevated BP at age 11. For molybdenum concentrations above the inflection points (~ 40–80 μg/L), positive associations with BP at age 4 were stronger at high levels of lead. Lead was positively associated with BP measures at age 4, but only at high levels of molybdenum. Potential interactions between molybdenum and lead were also identified for BP at age 11, but were sensitive to the cutoffs used to define elevated BP. Conclusions Prenatal exposure to high levels of molybdenum and lead, particularly in combination, may contribute to higher BP at age 4. These early effects appear to persist throughout childhood, contributing to elevated BP in adolescence. Future studies are needed to identify the major sources of molybdenum and lead in this population.
Caitlin G. Howe; Katerina Margetaki; Marina Vafeiadi; Theano Roumeliotaki; Marianna Karachaliou; Manolis Kogevinas; Rob McConnell; Sandrah P. Eckel; David V. Conti; Maria Kippler; Shohreh F. Farzan; Leda Chatzi. Prenatal metal mixtures and child blood pressure in the Rhea mother-child cohort in Greece. Environmental Health 2021, 20, 1 -16.
AMA StyleCaitlin G. Howe, Katerina Margetaki, Marina Vafeiadi, Theano Roumeliotaki, Marianna Karachaliou, Manolis Kogevinas, Rob McConnell, Sandrah P. Eckel, David V. Conti, Maria Kippler, Shohreh F. Farzan, Leda Chatzi. Prenatal metal mixtures and child blood pressure in the Rhea mother-child cohort in Greece. Environmental Health. 2021; 20 (1):1-16.
Chicago/Turabian StyleCaitlin G. Howe; Katerina Margetaki; Marina Vafeiadi; Theano Roumeliotaki; Marianna Karachaliou; Manolis Kogevinas; Rob McConnell; Sandrah P. Eckel; David V. Conti; Maria Kippler; Shohreh F. Farzan; Leda Chatzi. 2021. "Prenatal metal mixtures and child blood pressure in the Rhea mother-child cohort in Greece." Environmental Health 20, no. 1: 1-16.
Background:Reduced fetal growth increases the risk for adverse health outcomes. Growing evidence suggests that metal exposures contribute to reduced fetal growth, but little is known about the effects of complex metal mixtures.Objectives:We investigated the impact of a complex mixture of metals on birth weight for gestational age (BW for GA) in the Maternal and Developmental Risks from Environmental and Social Stressors study, a predominately lower-income Hispanic pregnancy cohort in Los Angeles, California.Methods:Cadmium (Cd), cobalt (Co), mercury (Hg), nickel (Ni), molybdenum (Mo), lead (Pb), antimony (Sb), tin (Sn), and thallium (Tl) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in early pregnancy (median GA: 13.1 wk). Speciated urinary arsenic (As) (inorganic+monomethyl+dimethyl As) was measured by high-performance liquid chromatography coupled to ICP-MS. Primary analyses focused on a mixture of seven metals that have previously been associated individually with fetal growth (i.e., As, Cd, Co, Hg, Ni, Pb, Tl) (n=262). In exploratory analyses, we additionally examined three metals that have been less studied in relation to fetal growth (i.e., Mo, Sb, Sn). Covariate-adjusted Bayesian kernel machine regression was used to investigate metal mixture associations with BW for GA z-scores.Results:In primary analyses, Hg and Ni ranked highest as predictors of BW for GA. An inverse linear association was estimated for Hg, whereas a positive association was estimated for Ni at low-to-moderate concentrations. A potential interaction between Hg and Ni was also identified. In our exploratory analysis, Sb ranked highest as a predictor of BW for GA, followed by Hg and Ni.Conclusions:Our findings suggest that in this understudied population, Hg may reduce fetal growth, whereas Ni may promote fetal growth. We also identified Sb as a potential metal of concern for this population, which merits additional investigation. https://doi.org/10.1289/EHP7201
Caitlin G. Howe; Birgit Claus Henn; Sandrah P. Eckel; Shohreh F. Farzan; Brendan H. Grubbs; Thomas A. Chavez; Tahlia L. Hodes; Dema Faham; Laila Al-Marayati; Deborah Lerner; Alyssa Quimby; Sara Twogood; Michael J. Richards; John D. Meeker; Theresa M. Bastain; Carrie V. Breton. Prenatal Metal Mixtures and Birth Weight for Gestational Age in a Predominately Lower-Income Hispanic Pregnancy Cohort in Los Angeles. Environmental Health Perspectives 2020, 128, 117001 .
AMA StyleCaitlin G. Howe, Birgit Claus Henn, Sandrah P. Eckel, Shohreh F. Farzan, Brendan H. Grubbs, Thomas A. Chavez, Tahlia L. Hodes, Dema Faham, Laila Al-Marayati, Deborah Lerner, Alyssa Quimby, Sara Twogood, Michael J. Richards, John D. Meeker, Theresa M. Bastain, Carrie V. Breton. Prenatal Metal Mixtures and Birth Weight for Gestational Age in a Predominately Lower-Income Hispanic Pregnancy Cohort in Los Angeles. Environmental Health Perspectives. 2020; 128 (11):117001.
Chicago/Turabian StyleCaitlin G. Howe; Birgit Claus Henn; Sandrah P. Eckel; Shohreh F. Farzan; Brendan H. Grubbs; Thomas A. Chavez; Tahlia L. Hodes; Dema Faham; Laila Al-Marayati; Deborah Lerner; Alyssa Quimby; Sara Twogood; Michael J. Richards; John D. Meeker; Theresa M. Bastain; Carrie V. Breton. 2020. "Prenatal Metal Mixtures and Birth Weight for Gestational Age in a Predominately Lower-Income Hispanic Pregnancy Cohort in Los Angeles." Environmental Health Perspectives 128, no. 11: 117001.
Epidemiologic evidence exists that many metals are associated with adverse neurobehavioral effects in young children, including lead (Pb), methylmercury (meHg), manganese (Mn), and arsenic (As) (Antunes dos Santos et al. J Trace Elem Med Biol. 38:99–107; Tolins et al. Ann Glob Health. 80(4):303–14; Vollet et al. Curr Environ Health Rep. 3(4):392–404; Bellinger Curr Opin Pediatr. 20(2):172–7). Importantly, chemical insult can vary depending on host factors and exposure circumstance. This systematic review summarizes the recent literature investigating modifying factors of the associations between metals and neurodevelopment, including immutable traits (sex or genetics) or exposure conditions (timing or co-exposures). Of the 53 studies included in this review, the number investigating the modification of exposure effects was as follows: 30 for sex, 21 for co-exposures, 12 for timing of exposure, and six for genetic modifiers. Sex-specific effects of metal-neurobehavioral associations were inconclusive for all metals, likely due to the heterogeneity of outcome domains assessed and the exposure time points measured. Seven studies evaluated both sex and exposure timing as modifying factors using deciduous teeth or other biomarkers with repeated measures to characterize metals exposure over time. Only five studies used statistical methods for mixtures to evaluate associations of more than two metals with neurobehavioral domains. Despite the expansion of research on susceptibility to the neurodevelopmental effects of metals exposure, considerable gaps remain. This work remains critical, as characterizing susceptible subpopulations can aid in identifying biological mechanisms and is fundamental for the protection of public health.
Julia A. Bauer; Victoria Fruh; Caitlin G. Howe; Roberta F. White; Birgit Claus Henn. Associations of Metals and Neurodevelopment: a Review of Recent Evidence on Susceptibility Factors. Current Epidemiology Reports 2020, 7, 237 -262.
AMA StyleJulia A. Bauer, Victoria Fruh, Caitlin G. Howe, Roberta F. White, Birgit Claus Henn. Associations of Metals and Neurodevelopment: a Review of Recent Evidence on Susceptibility Factors. Current Epidemiology Reports. 2020; 7 (4):237-262.
Chicago/Turabian StyleJulia A. Bauer; Victoria Fruh; Caitlin G. Howe; Roberta F. White; Birgit Claus Henn. 2020. "Associations of Metals and Neurodevelopment: a Review of Recent Evidence on Susceptibility Factors." Current Epidemiology Reports 7, no. 4: 237-262.
Fetal growth is predictive of health later in life. Both toxic and essential metals influence fetal growth, but most studies have focused on these elements individually and used birth weight as an indicator of fetal growth. The objective of the current study was to investigate the impact of a mixture of metals on fetal size in mid-pregnancy in a predominately lower income Hispanic pregnancy cohort in Los Angeles. For our primary analysis, we focused on six elements that have previously been associated individually with fetal size, including arsenic (As), barium (Ba), cadmium (Cd), mercury (Hg), molybdenum (Mo), and tin (Sn), measured in maternal urine samples collected in early pregnancy (median: 12.4 weeks gestation). In an exploratory analysis, we additionally included cobalt (Co), nickel (Ni), antimony (Sb), and thallium (Tl). Using covariate-adjusted Bayesian Kernel Machine Regression (BKMR) as our main mixture modeling approach, we examined the impact of these metals on fetal biometry measures obtained between 18 and 22 weeks gestation, with a focus on estimated fetal weight (EFW). BKMR identified Mo and Ba as the mixture components that contributed most to associations with EFW. Linear associations were observed for both metals. An increase in Mo from the 25th to 75th percentile was associated with a 0.114 (95% credible interval (CI): 0.019, 0.247) SD higher EFW, equivalent to a 7.4 g difference. Similar associations were observed between Mo and the other fetal measures evaluated. In contrast, an increase in Ba from the 25th to 75th percentile was associated with a −0.076 (95% CI: 0.217, 0.066) SD lower EFW, equivalent to a 4.9 g difference. Similar inverse associations were observed for Ba in relation to abdominal circumference and biparietal diameter. BKMR also identified a possible interaction between Ba and Mo in relation to head circumference, suggesting that the positive associations between Mo and this outcome may be attenuated at high levels of Ba, which was consistent with findings from linear regression (Pinteraction = 0.03). In an exploratory analysis accounting for a larger mixture of metals, Mo and Ba consistently contributed most to associations with EFW. An inverse association was also identified between Sb and EFW. Our results suggest that Mo may promote fetal growth, while Ba and Sb may reduce fetal growth, in this population.
Caitlin G. Howe; Birgit Claus Henn; Shohreh F. Farzan; Rima Habre; Sandrah P. Eckel; Brendan H. Grubbs; Thomas A. Chavez; Dema Faham; Laila Al-Marayati; Deborah Lerner; Alyssa Quimby; Sara Twogood; Michael J. Richards; John D. Meeker; Theresa M. Bastain; Carrie V. Breton. Prenatal metal mixtures and fetal size in mid-pregnancy in the MADRES study. Environmental Research 2020, 196, 110388 .
AMA StyleCaitlin G. Howe, Birgit Claus Henn, Shohreh F. Farzan, Rima Habre, Sandrah P. Eckel, Brendan H. Grubbs, Thomas A. Chavez, Dema Faham, Laila Al-Marayati, Deborah Lerner, Alyssa Quimby, Sara Twogood, Michael J. Richards, John D. Meeker, Theresa M. Bastain, Carrie V. Breton. Prenatal metal mixtures and fetal size in mid-pregnancy in the MADRES study. Environmental Research. 2020; 196 ():110388.
Chicago/Turabian StyleCaitlin G. Howe; Birgit Claus Henn; Shohreh F. Farzan; Rima Habre; Sandrah P. Eckel; Brendan H. Grubbs; Thomas A. Chavez; Dema Faham; Laila Al-Marayati; Deborah Lerner; Alyssa Quimby; Sara Twogood; Michael J. Richards; John D. Meeker; Theresa M. Bastain; Carrie V. Breton. 2020. "Prenatal metal mixtures and fetal size in mid-pregnancy in the MADRES study." Environmental Research 196, no. : 110388.
Methylation of ingested inorganic arsenic (InAs) to monomethyl- (MMAs) and dimethyl-arsenical species (DMAs) facilitates urinary arsenic elimination. Folate and creatine supplementation influenced arsenic methylation in a randomized controlled trial. Here, we examine if baseline status of one-carbon metabolism nutrients (folate, choline, betaine, and vitamin B12) modified the effects of FA and creatine supplementation on changes in homocysteine, guanidinoacetate (GAA), total blood arsenic, and urinary arsenic metabolite proportions and indices. Study participants (N = 622) received 400 or 800 μg FA, 3 g creatine, 400 μg FA + 3 g creatine, or placebo daily for 12 weeks. Relative to placebo, FA supplementation was associated with greater mean increases in %DMAs among participants with betaine concentrations below the median than those with levels above the median (FDR < 0.05). 400 μg FA/day was associated with a greater decrease in homocysteine among participants with plasma folate concentrations below, compared with those above, the median (FDR < 0.03). Creatine treatment was associated with a significant decrease in %MMAs among participants with choline concentrations below the median (P = 0.04), but not among participants above the median (P = 0.94); this effect did not significantly differ between strata (P = 0.10). Effects of FA and creatine supplementation on arsenic methylation capacity were greater among individuals with low betaine and choline status, respectively. The efficacy of FA and creatine interventions to facilitate arsenic methylation may be modified by choline and betaine nutritional status. Clinical Trial Registry Identifier: NCT01050556, U.S. National Library of Medicine, https://clinicaltrials.gov; registered January 15, 2010.
Anne K. Bozack; Caitlin G. Howe; Megan N. Hall; Xinhua Liu; Vesna Slavkovich; Vesna Ilievski; Angela M. Lomax-Luu; Faruque Parvez; Abu B. Siddique; Hasan Shahriar; Mohammad N. Uddin; Tariqul Islam; Joseph H. Graziano; Mary V. Gamble. Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults. European Journal of Nutrition 2020, 60, 1921 -1934.
AMA StyleAnne K. Bozack, Caitlin G. Howe, Megan N. Hall, Xinhua Liu, Vesna Slavkovich, Vesna Ilievski, Angela M. Lomax-Luu, Faruque Parvez, Abu B. Siddique, Hasan Shahriar, Mohammad N. Uddin, Tariqul Islam, Joseph H. Graziano, Mary V. Gamble. Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults. European Journal of Nutrition. 2020; 60 (4):1921-1934.
Chicago/Turabian StyleAnne K. Bozack; Caitlin G. Howe; Megan N. Hall; Xinhua Liu; Vesna Slavkovich; Vesna Ilievski; Angela M. Lomax-Luu; Faruque Parvez; Abu B. Siddique; Hasan Shahriar; Mohammad N. Uddin; Tariqul Islam; Joseph H. Graziano; Mary V. Gamble. 2020. "Betaine and choline status modify the effects of folic acid and creatine supplementation on arsenic methylation in a randomized controlled trial of Bangladeshi adults." European Journal of Nutrition 60, no. 4: 1921-1934.
Prenatal arsenic exposure has been associated with reduced fetal growth and increased risk for preterm birth, but most studies have been conducted in highly exposed populations outside the U.S. or in non-Hispanic populations in the rural U.S. The objectives of the current study were to: 1) examine the impact of early pregnancy exposure to arsenic on birth weight and gestational age at birth in a predominately lower income Hispanic pregnancy cohort in urban Los Angeles and 2) compare multiple biomarkers of arsenic exposure (blood, urine, and hair) assessed in early pregnancy (mean ± SD gestational age at biospecimen collection: 14 ± 4 weeks). Total arsenic (blood, hair) was measured by ICP-MS and speciated arsenic (urine) was measured by HPLC coupled to ICP-MS. Associations between log2-transformed arsenic measures and birth outcomes were evaluated using multivariable linear regression. A doubling in hair arsenic was associated with a 72.2 g (95% CI: −144.3, −0.1, P = 0.05) lower birth weight, after adjusting for potential confounders and gestational age at birth. A similar but non-significant trend was observed for blood arsenic, but not urine arsenic. The inverse association between hair arsenic and birth weight was more pronounced among infants whose mothers gained greater amounts of weight during pregnancy (Pinteraction = 0.02). The association between urinary monomethyl arsenic and GA at birth differed by pre-pregnancy BMI (Pinteraction<0.01). This study provides evidence that even at relatively low levels of exposure, arsenic exposure (measured in hair samples collected in early pregnancy) may adversely affect fetal growth in this understudied population, particularly in combination with greater gestational weight gain. Future studies with larger sample sizes are needed to confirm these findings and to further investigate some of the inconsistencies observed for the different arsenic biomarkers evaluated.
Caitlin G. Howe; Shohreh F. Farzan; Erika Garcia; Thomas Jursa; Ramsunder Iyer; Kiros Berhane; Thomas A. Chavez; Tahlia L. Hodes; Brendan H. Grubbs; William E. Funk; Donald R. Smith; Theresa M. Bastain; Carrie V. Breton. Arsenic and birth outcomes in a predominately lower income Hispanic pregnancy cohort in Los Angeles. Environmental Research 2020, 184, 109294 -109294.
AMA StyleCaitlin G. Howe, Shohreh F. Farzan, Erika Garcia, Thomas Jursa, Ramsunder Iyer, Kiros Berhane, Thomas A. Chavez, Tahlia L. Hodes, Brendan H. Grubbs, William E. Funk, Donald R. Smith, Theresa M. Bastain, Carrie V. Breton. Arsenic and birth outcomes in a predominately lower income Hispanic pregnancy cohort in Los Angeles. Environmental Research. 2020; 184 ():109294-109294.
Chicago/Turabian StyleCaitlin G. Howe; Shohreh F. Farzan; Erika Garcia; Thomas Jursa; Ramsunder Iyer; Kiros Berhane; Thomas A. Chavez; Tahlia L. Hodes; Brendan H. Grubbs; William E. Funk; Donald R. Smith; Theresa M. Bastain; Carrie V. Breton. 2020. "Arsenic and birth outcomes in a predominately lower income Hispanic pregnancy cohort in Los Angeles." Environmental Research 184, no. : 109294-109294.
OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345–248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870–135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate–adjusted P value threshold of 0.05. CONCLUSIONS Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.
Caitlin G. Howe; Bianca Cox; Ruby Fore; James Jungius; Tuomas Kvist; Samantha Lent; Harriet E. Miles; Lucas A Salas; Sheryl Rifas-Shiman; Anne P. Starling; Paul Yousefi; Christine Ladd-Acosta; Andrea Baccarelli; Elisabeth B. Binder; Vaia Lida Chatzi; Darina Czamara; Dana Dabelea; Dawn L. DeMeo; Akram Ghantous; Zdenko Herceg; Eero Kajantie; Jari Lahti; Debbie A. Lawlor; Augusto Litonjua; Tim Nawrot; Ellen A. Nohr; Emily Oken; Costanza Pizzi; Michelle Plusquin; Katri Räikkönen; Caroline Relton; Gemma Sharp; Thorkild I.A. Sørensen; Jordi Sunyer; Martine Vrijheid; Weiming Zhang; Marie-France Hivert; Carrie V. Breton. Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium. Diabetes Care 2019, 43, 98 -105.
AMA StyleCaitlin G. Howe, Bianca Cox, Ruby Fore, James Jungius, Tuomas Kvist, Samantha Lent, Harriet E. Miles, Lucas A Salas, Sheryl Rifas-Shiman, Anne P. Starling, Paul Yousefi, Christine Ladd-Acosta, Andrea Baccarelli, Elisabeth B. Binder, Vaia Lida Chatzi, Darina Czamara, Dana Dabelea, Dawn L. DeMeo, Akram Ghantous, Zdenko Herceg, Eero Kajantie, Jari Lahti, Debbie A. Lawlor, Augusto Litonjua, Tim Nawrot, Ellen A. Nohr, Emily Oken, Costanza Pizzi, Michelle Plusquin, Katri Räikkönen, Caroline Relton, Gemma Sharp, Thorkild I.A. Sørensen, Jordi Sunyer, Martine Vrijheid, Weiming Zhang, Marie-France Hivert, Carrie V. Breton. Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium. Diabetes Care. 2019; 43 (1):98-105.
Chicago/Turabian StyleCaitlin G. Howe; Bianca Cox; Ruby Fore; James Jungius; Tuomas Kvist; Samantha Lent; Harriet E. Miles; Lucas A Salas; Sheryl Rifas-Shiman; Anne P. Starling; Paul Yousefi; Christine Ladd-Acosta; Andrea Baccarelli; Elisabeth B. Binder; Vaia Lida Chatzi; Darina Czamara; Dana Dabelea; Dawn L. DeMeo; Akram Ghantous; Zdenko Herceg; Eero Kajantie; Jari Lahti; Debbie A. Lawlor; Augusto Litonjua; Tim Nawrot; Ellen A. Nohr; Emily Oken; Costanza Pizzi; Michelle Plusquin; Katri Räikkönen; Caroline Relton; Gemma Sharp; Thorkild I.A. Sørensen; Jordi Sunyer; Martine Vrijheid; Weiming Zhang; Marie-France Hivert; Carrie V. Breton. 2019. "Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium." Diabetes Care 43, no. 1: 98-105.
Maternal tobacco smoke exposure has been associated with altered DNA methylation. However, previous studies largely used methylation arrays, which cover a small fraction of CpGs, and focused on whole cord blood. The current study examined the impact of in utero exposure to maternal tobacco smoke on the cord blood CD4+ DNA methylome. The methylomes of 20 Hispanic white newborns (n=10 exposed to any maternal tobacco smoke in pregnancy; n=10 unexposed) from the Maternal and Child Health Study (MACHS) were profiled by whole-genome bisulfite sequencing (median coverage: 6.5×). Statistical analyses were conducted using the Regression Analysis of Differential Methylation (RADMeth) program because it performs well on low-coverage data (minimizes false positives and negatives). We found that 10,381 CpGs were differentially methylated by tobacco smoke exposure [neighbor-adjusted p-values that are additionally corrected for multiple testing based on the Benjamini-Hochberg method for controlling the false discovery rate (FDR) (pFDR)<0.05]. From these CpGs, RADMeth identified 557 differentially methylated regions (DMRs) that were overrepresented (p<0.05) in important regulatory regions, including enhancers. Of nine DMRs that could be queried in a reduced representation bisulfite sequencing (RRBS) study of adult CD4+ cells (n=9 smokers; n=10 nonsmokers), four replicated (p<0.05). Additionally, a CpG in the promoter of SLC7A8 (percent methylation difference: −9.4% comparing exposed to unexposed) replicated (p<0.05) in an EPIC (Illumina) array study of cord blood CD4+ cells (n=14 exposed to sustained maternal tobacco smoke; n=16 unexposed) and in a study of adult CD4+ cells across two platforms (EPIC: n=9 smokers; n=11 nonsmokers; 450K: n=59 smokers; n=72 nonsmokers). Maternal tobacco smoke exposure in pregnancy is associated with cord blood CD4+ DNA methylation in key regulatory regions, including enhancers. While we used a method that performs well on low-coverage data, we cannot exclude the possibility that some results may be false positives. However, we identified a differentially methylated CpG in amino acid transporter SLC7A8 that is highly reproducible, which may be sensitive to cigarette smoke in both cord blood and adult CD4+ cells. https://doi.org/10.1289/EHP3398
Caitlin Howe; Meng Zhou; Xuting Wang; Gary S. Pittman; Isabel J. Thompson; Michelle R. Campbell; Theresa M. Bastain; Brendan H. Grubbs; Muhammad T. Salam; Cathrine Hoyo; Uglas A. Bell; Andrew D. Smith; Carrie V. Breton. Associations between Maternal Tobacco Smoke Exposure and the Cord Blood CD4+ DNA Methylome. Environmental Health Perspectives 2019, 127, 47009 .
AMA StyleCaitlin Howe, Meng Zhou, Xuting Wang, Gary S. Pittman, Isabel J. Thompson, Michelle R. Campbell, Theresa M. Bastain, Brendan H. Grubbs, Muhammad T. Salam, Cathrine Hoyo, Uglas A. Bell, Andrew D. Smith, Carrie V. Breton. Associations between Maternal Tobacco Smoke Exposure and the Cord Blood CD4+ DNA Methylome. Environmental Health Perspectives. 2019; 127 (4):47009.
Chicago/Turabian StyleCaitlin Howe; Meng Zhou; Xuting Wang; Gary S. Pittman; Isabel J. Thompson; Michelle R. Campbell; Theresa M. Bastain; Brendan H. Grubbs; Muhammad T. Salam; Cathrine Hoyo; Uglas A. Bell; Andrew D. Smith; Carrie V. Breton. 2019. "Associations between Maternal Tobacco Smoke Exposure and the Cord Blood CD4+ DNA Methylome." Environmental Health Perspectives 127, no. 4: 47009.
RationaleWe aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.MethodsWe meta-analysed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio and forced expiratory flow at 75% of FVC at ages 7–13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.ResultsWe identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and nine with COPD in adulthood. Genes annotated to the top 10 identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.InterpretationOur findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.
Herman T. Den Dekker; Kimberley Burrows; Janine F. Felix; Lucas A. Salas; Ivana Nedeljkovic; Jin Yao; Sheryl L. Rifas-Shiman; Carlos Ruiz-Arenas; N. Amin; Mariona Bustamante; Dawn L. DeMeo; A. John Henderson; Caitlin Howe; Marie-France Hivert; M. Arfan Ikram; Johan C. De Jongste; Lies LaHousse; Pooja R. Mandaviya; Joyce B. Van Meurs; Mariona Pinart; Gemma Sharp; Lisette Stolk; André G. Uitterlinden; Josep M. Anto; Augusto A. Litonjua; Carrie V. Breton; Guy Brusselle; Jordi Sunyer; George Davey Smith; Caroline Relton; Vincent W.V. Jaddoe; Liesbeth Duijts. Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course. European Respiratory Journal 2019, 53, 1801795 .
AMA StyleHerman T. Den Dekker, Kimberley Burrows, Janine F. Felix, Lucas A. Salas, Ivana Nedeljkovic, Jin Yao, Sheryl L. Rifas-Shiman, Carlos Ruiz-Arenas, N. Amin, Mariona Bustamante, Dawn L. DeMeo, A. John Henderson, Caitlin Howe, Marie-France Hivert, M. Arfan Ikram, Johan C. De Jongste, Lies LaHousse, Pooja R. Mandaviya, Joyce B. Van Meurs, Mariona Pinart, Gemma Sharp, Lisette Stolk, André G. Uitterlinden, Josep M. Anto, Augusto A. Litonjua, Carrie V. Breton, Guy Brusselle, Jordi Sunyer, George Davey Smith, Caroline Relton, Vincent W.V. Jaddoe, Liesbeth Duijts. Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course. European Respiratory Journal. 2019; 53 (4):1801795.
Chicago/Turabian StyleHerman T. Den Dekker; Kimberley Burrows; Janine F. Felix; Lucas A. Salas; Ivana Nedeljkovic; Jin Yao; Sheryl L. Rifas-Shiman; Carlos Ruiz-Arenas; N. Amin; Mariona Bustamante; Dawn L. DeMeo; A. John Henderson; Caitlin Howe; Marie-France Hivert; M. Arfan Ikram; Johan C. De Jongste; Lies LaHousse; Pooja R. Mandaviya; Joyce B. Van Meurs; Mariona Pinart; Gemma Sharp; Lisette Stolk; André G. Uitterlinden; Josep M. Anto; Augusto A. Litonjua; Carrie V. Breton; Guy Brusselle; Jordi Sunyer; George Davey Smith; Caroline Relton; Vincent W.V. Jaddoe; Liesbeth Duijts. 2019. "Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course." European Respiratory Journal 53, no. 4: 1801795.
Growing evidence suggests that environmental exposures can influence blood pressure over the course of a lifetime. Exposure to toxic metals, such as lead (Pb) and arsenic (As), has been associated with increased blood pressure in adults, but few studies have examined the impacts of in utero and early life toxic metals exposure on blood pressure in childhood. As subclinical vascular changes are thought to begin early in life, it is possible that in utero toxic metals exposure may play a role in blood pressure homeostasis. In the ongoing New Hampshire Birth Cohort Study, we investigated whether in utero exposure to Pb and As was associated with measures of blood pressure in a total of 323 young children (mean age 5.5 years, SD 0.4). Pb and As were measured in maternal toenail samples collected at ~28 weeks gestation (n = 257) and/or 6 weeks postpartum (n = 285), which represent exposures ~6 to 12 months prior to collection and therefore reflect the early prenatal and late prenatal exposures, respectively. Five measurements of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were averaged for each child using a standardized technique. In linear regression analyses, where log2-transformed prenatal toenail Pb and As were modeled jointly and adjusted for child age, sex, height, weight and maternal smoking during pregnancy, we observed that a doubling of maternal prenatal toenail Pb was associated with statistically significant increases in child SBP (β: 0.58 mm Hg, 95% CI: 0.05, 1.11). We did not observe any association of prenatal or postpartum As, or postpartum Pb, with SBP or DBP. Exploratory sex-stratified analyses suggest that associations of prenatal Pb with BP may be stronger among boys (SBP β: 0.72 mm Hg: 95% CI: −0.01, 1.44; DBP β: 0.37; 95% CI: −0.09, 0.84), compared to girls (SBP β: 0.48 mm Hg: 95% CI: −0.31, 1.26; DBP β: −0.05; 95% CI: −0.52, 0.41), though tests for interaction did not reach statistical significance (p-interaction SBP = 0.059; DBP = 0.057). Our preliminary results suggest that in utero toxic metals exposures may be associated with early life increases in blood pressure in children, which could have consequences for long-term health.
Shohreh F. Farzan; Caitlin Howe; Yu Chen; Diane Gilbert-Diamond; Kathryn Cottingham; Brian P. Jackson; Adam R. Weinstein; Margaret R. Karagas. Prenatal lead exposure and elevated blood pressure in children. Environment International 2018, 121, 1289 -1296.
AMA StyleShohreh F. Farzan, Caitlin Howe, Yu Chen, Diane Gilbert-Diamond, Kathryn Cottingham, Brian P. Jackson, Adam R. Weinstein, Margaret R. Karagas. Prenatal lead exposure and elevated blood pressure in children. Environment International. 2018; 121 ():1289-1296.
Chicago/Turabian StyleShohreh F. Farzan; Caitlin Howe; Yu Chen; Diane Gilbert-Diamond; Kathryn Cottingham; Brian P. Jackson; Adam R. Weinstein; Margaret R. Karagas. 2018. "Prenatal lead exposure and elevated blood pressure in children." Environment International 121, no. : 1289-1296.
Prenatal PM exposure, particularly in early pregnancy and midpregnancy, is associated with higher newborn TT4 concentrations. Future studies should assess the health implications of PM-associated differences in newborn TT4 concentrations.
Caitlin Howe; Sandrah P. Eckel; Rima Habre; Mariam S. Girguis; Lu Gao; Frederick W. Lurmann; Frank D. Gilliland; Carrie V. Breton. Association of Prenatal Exposure to Ambient and Traffic-Related Air Pollution With Newborn Thyroid Function. JAMA Network Open 2018, 1, e182172 .
AMA StyleCaitlin Howe, Sandrah P. Eckel, Rima Habre, Mariam S. Girguis, Lu Gao, Frederick W. Lurmann, Frank D. Gilliland, Carrie V. Breton. Association of Prenatal Exposure to Ambient and Traffic-Related Air Pollution With Newborn Thyroid Function. JAMA Network Open. 2018; 1 (5):e182172.
Chicago/Turabian StyleCaitlin Howe; Sandrah P. Eckel; Rima Habre; Mariam S. Girguis; Lu Gao; Frederick W. Lurmann; Frank D. Gilliland; Carrie V. Breton. 2018. "Association of Prenatal Exposure to Ambient and Traffic-Related Air Pollution With Newborn Thyroid Function." JAMA Network Open 1, no. 5: e182172.
Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) supports oncogenic signaling in a number of solid and hematologic tumors. Little is known about the role of NEDD9 in ovarian carcinoma (OC), but available data suggest elevated mRNA and protein expression in advanced stage high-grade cancers. We used a transgenic MISIIR-TAg mouse OC model combined with genetic ablation of Nedd9 to investigate its action in the development and progression of OC. A Nedd9−/− genotype delayed tumor growth rate, reduced incidence of ascites, and reduced expression and activation of signaling proteins including SRC, STAT3, E-cadherin, and AURKA. Cell lines established from MISIIR-TAg;Nedd9−/− and MISIIR-TAg;Nedd9+/+ mice exhibited altered migration and invasion. Growth of these cells in a syngeneic allograft model indicated that systemic Nedd9 loss in the microenvironment had little impact on tumor allograft growth, but in a Nedd9 wild-type background Nedd9−/− allografts exhibited significantly reduced growth, dissemination, and oncogenic signaling compared to Nedd9+/+ allografts. Gene expression analysis revealed that Nedd9+/+ tumors exhibited more mesenchymal “stem-like” transcriptional program, including increased expression of Aldh1a1 and Aldh1a2. Conversely, loss of Nedd9 resulted in increased expression of differentiation genes, including fallopian tube markers Foxj1, Ovgp1, and Pax8. Collectively, these data suggest that tumor cell-intrinsic Nedd9 expression promotes OC development and progression by broad induction of oncogenic protein signaling and stem/mesenchymal gene expression.
Rashid Gabbasov; Fang. Xiao; Caitlin Howe; Laura E. Bickel; Shane W. O’Brien; Daniel Benrubi; Thuy-Vy Do; Yan Zhou; Emmanuelle Nicolas; Kathy Q. Cai; Samuel Litwin; Sachiko Seo; Erica A. Golemis; Denise C. Connolly. NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice. Oncogene 2018, 37, 4854 -4870.
AMA StyleRashid Gabbasov, Fang. Xiao, Caitlin Howe, Laura E. Bickel, Shane W. O’Brien, Daniel Benrubi, Thuy-Vy Do, Yan Zhou, Emmanuelle Nicolas, Kathy Q. Cai, Samuel Litwin, Sachiko Seo, Erica A. Golemis, Denise C. Connolly. NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice. Oncogene. 2018; 37 (35):4854-4870.
Chicago/Turabian StyleRashid Gabbasov; Fang. Xiao; Caitlin Howe; Laura E. Bickel; Shane W. O’Brien; Daniel Benrubi; Thuy-Vy Do; Yan Zhou; Emmanuelle Nicolas; Kathy Q. Cai; Samuel Litwin; Sachiko Seo; Erica A. Golemis; Denise C. Connolly. 2018. "NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice." Oncogene 37, no. 35: 4854-4870.
Arsenic (As) exposure has been associated with increased risk for cardiovascular disease (CVD) and with biomarkers of potential CVD risk and inflammatory processes. However, few studies have evaluated the effects of As on such biomarkers in U.S. populations, which are typically exposed to low to moderate As concentrations. We investigated associations between As exposures and biomarkers relevant to inflammation, oxidative stress, and CVD risk in a subset of participants from the New Hampshire Health Study, a population with low to moderate As exposure (n=418). Associations between toenail As, total urine As (uAs), and %uAs metabolites [monomethyl (%uMMAV), dimethyl (%uDMAV), and inorganic (%iAs) species] and plasma biomarkers, including soluble plasma vascular and cellular adhesion molecules (VCAM-1 and ICAM-1, respectively), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α, plasminogen activator inhibitor-1 (PAI-1), and urinary oxidative stress marker 15-F2t-isoprostane (15-F2t-IsoP), were evaluated using linear regression models. Covariate-adjusted estimates of associations with a doubling of urinary As suggested an 8.8% increase in 15-F2t-IsoP (95% CI: 3.2, 14.7), and a doubling of toenail As was associated with a 1.7% increase in VCAM-1 (95% CI: 0.2, 3.2). Additionally, a 5% increase in %uMMA was associated with a 7.9% increase in 15-F2t-IsoP (95% CI: 2.1, 14.1), and a 5% increase in %uDMA was associated with a 2.98% decrease in 15-F2t-IsoP [(95% CI: −6.1, 0.21); p=0.07]. However, in contrast with expectations, a doubling of toenail As was associated with a 2.3% decrease (95% CI: −4.3, −0.3) in MMP-9, and a 5% increase in %uMMA was associated with a 7.7% decrease (95% CI: −12.6, −2.5) in PAI-1. In a cross-sectional study of U.S. adults, we observed some positive associations of uAs and toenail As concentrations with biomarkers potentially relevant to CVD pathogenesis and inflammation, and evidence of a higher capacity to metabolize inorganic As was negatively associated with a marker of oxidative stress. https://doi.org/10.1289/EHP2062
Shohreh F. Farzan; Caitlin G. Howe; Michael S. Zens; Thomas Palys; Jacqueline Y. Channon; Zhigang Li; Yu Chen; Margaret R. Karagas. Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: A Cross-Sectional Study. Environmental Health Perspectives 2017, 125, 127002 .
AMA StyleShohreh F. Farzan, Caitlin G. Howe, Michael S. Zens, Thomas Palys, Jacqueline Y. Channon, Zhigang Li, Yu Chen, Margaret R. Karagas. Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: A Cross-Sectional Study. Environmental Health Perspectives. 2017; 125 (12):127002.
Chicago/Turabian StyleShohreh F. Farzan; Caitlin G. Howe; Michael S. Zens; Thomas Palys; Jacqueline Y. Channon; Zhigang Li; Yu Chen; Margaret R. Karagas. 2017. "Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: A Cross-Sectional Study." Environmental Health Perspectives 125, no. 12: 127002.
Background: Arsenic exposure has been associated with an increased risk of cardiovascular disease (CVD). Growing evidence suggests that B vitamins facilitate arsenic metabolism and may protect against arsenic toxicity. However, to our knowledge, few studies have evaluated this in US populations. Objective: Our objective was to examine whether higher B vitamin intake is associated with enhanced arsenic metabolism and lower concentrations of preclinical markers of CVD among New Hampshire adults. Methods: We used weighted quantile sum (WQS) regression to evaluate the collective impact of 6 dietary B vitamins (thiamin, riboflavin, folate, niacin, and vitamins B-6 and B-12) on 1) the proportion of arsenic metabolites in urine and 2) 6 CVD-related markers [including urinary 15-F2t-isoprostane (15-F2t-IsoP)] among 418 participants (26–75 y of age) from the New Hampshire Health Study. Contributions of arsenic metabolites to B vitamin-CVD marker associations were also explored in structural equation models. Results: In WQS models, the weighted sum of B vitamin intakes from food sources was inversely associated with the proportion of monomethyl arsenic species in urine (uMMA) (β: −1.03; 95% CI: −1.91, −0.15; P = 0.02). Thiamin and vitamins B-6 and B-12 contributed the most to this association, whereas riboflavin had a negligible effect. Higher overall B vitamin intake was also inversely associated with 15-F2t-IsoP (β: −0.21; 95% CI: −0.32, −0.11; P < 0.01), with equal contributions from the 6 B vitamins, which was partially explained by differences in the proportion of uMMA (indirect effect β: −0.01; 95% CI: −0.04, −0.00). Conclusions: Among New Hampshire adults, higher intakes of certain B vitamins (particularly thiamin and vitamins B-6 and B-12 from food sources) may reduce the proportion of uMMA, an intermediate of arsenic metabolism that has been associated with an increased risk of CVD. Higher overall B vitamin intake may also reduce urinary 15-F2t-IsoP, a marker of oxidative stress and potential risk factor for CVD, in part by reducing the proportion of uMMA.
Caitlin G Howe; Zhigang Li; Michael S Zens; Thomas Palys; Yu Chen; Jacqueline Y Channon; Margaret R Karagas; Shohreh F Farzan. Dietary B Vitamin Intake Is Associated with Lower Urinary Monomethyl Arsenic and Oxidative Stress Marker 15-F2t-Isoprostane among New Hampshire Adults. The Journal of Nutrition 2017, 147, 2289 -2296.
AMA StyleCaitlin G Howe, Zhigang Li, Michael S Zens, Thomas Palys, Yu Chen, Jacqueline Y Channon, Margaret R Karagas, Shohreh F Farzan. Dietary B Vitamin Intake Is Associated with Lower Urinary Monomethyl Arsenic and Oxidative Stress Marker 15-F2t-Isoprostane among New Hampshire Adults. The Journal of Nutrition. 2017; 147 (12):2289-2296.
Chicago/Turabian StyleCaitlin G Howe; Zhigang Li; Michael S Zens; Thomas Palys; Yu Chen; Jacqueline Y Channon; Margaret R Karagas; Shohreh F Farzan. 2017. "Dietary B Vitamin Intake Is Associated with Lower Urinary Monomethyl Arsenic and Oxidative Stress Marker 15-F2t-Isoprostane among New Hampshire Adults." The Journal of Nutrition 147, no. 12: 2289-2296.
Accumulating evidence indicates that arsenic (As), a potent environmental toxicant, may increase cardiovascular disease risk and adversely affect endothelial function at high levels of exposure. Pregnancy is a vulnerable time for both mother and child; however, studies examining the association between prenatal As exposure and plasma biomarkers of inflammation and endothelial function in mothers and newborns are lacking. We examined maternal urinary As levels at gestational weeks 24–28 and levels of inflammatory biomarkers in plasma from 563 pregnant women and 500 infants’ cord blood. We assessed a multiplexed panel of circulating inflammatory and endothelial function markers, including tumor necrosis factor alpha (TNFα), monocyte chemoattractant protein 1 (MCP1), intercellular adhesion molecule (ICAM1) and vascular cell adhesion molecule (VCAM1). Compared with the bottom tertile, the highest tertile of maternal urinary As during pregnancy was associated with a 145.2 ng/ml (95% CI 4.1, 286.3; p=0.04) increase in cord blood ICAM1 and 557.3 ng/ml (95% CI −56.4, 1171.1; p=0.09) increase in cord blood VCAM1. Among mothers, the highest tertile of maternal urinary As during pregnancy was related to a 141.8 ng/ml (95% CI 26.1, 257.5; p=0.02) increase maternal plasma VCAM1 levels. Urinary As was unrelated to MCP1 or TNFα in maternal plasma and cord blood. In structural equation models, the association between maternal urinary As and infant VCAM was mediated by maternal levels of VCAM (βmediation: 0.024, 95% CI: 0.002, 0.050). Our observations indicate that As exposure during pregnancy may affect markers of vascular health and endothelial function in both pregnant women and children, and suggest further investigation of the potential impacts on cardiovascular health in these susceptible populations.
Shohreh F. Farzan; Elizabeth B. Brickley; Zhigang Li; Diane Gilbert-Diamond; Anala Gossai; Yu Chen; Caitlin G. Howe; Thomas Palys; Margaret R. Karagas. Maternal and infant inflammatory markers in relation to prenatal arsenic exposure in a U.S. pregnancy cohort. Environmental Research 2017, 156, 426 -433.
AMA StyleShohreh F. Farzan, Elizabeth B. Brickley, Zhigang Li, Diane Gilbert-Diamond, Anala Gossai, Yu Chen, Caitlin G. Howe, Thomas Palys, Margaret R. Karagas. Maternal and infant inflammatory markers in relation to prenatal arsenic exposure in a U.S. pregnancy cohort. Environmental Research. 2017; 156 ():426-433.
Chicago/Turabian StyleShohreh F. Farzan; Elizabeth B. Brickley; Zhigang Li; Diane Gilbert-Diamond; Anala Gossai; Yu Chen; Caitlin G. Howe; Thomas Palys; Margaret R. Karagas. 2017. "Maternal and infant inflammatory markers in relation to prenatal arsenic exposure in a U.S. pregnancy cohort." Environmental Research 156, no. : 426-433.
Crustaceans (decapods, isopods and amphipods) are recent colonists of land and range from amphibious to terrestrial species. The majority of terrestrial crustaceans, like their aquatic ancestors, have retained ammonotely. Amphibious species periodically return to standing pools of water to excrete ammonia, via the gills. In more terrestrial species, ammonia is eliminated in either an excretory fluid such as urine or P or volatilised as a gas. Due to the potential toxicity of ammonia, waste nitrogen is stored as transaminated amino acids such as glutamate, glutamine and glycine, between excretory bouts. Only one species, Birgus latro is known to be primarily purinotelic, producing a white faecal pellet of guanine and uric acid. Numerous terrestrial isopod and decapod crustaceans do, however, possess solid purine deposits of urate which are stored intracellularly within spongy connective tissue cells. The urate is synthesised de novo from excess dietary nitrogen. The deposits have been suggested to function as either storage excretion or to act as a temporary nitrogen store. In decapod crustaceans, there is substantial evidence against the temporary nitrogen store hypothesis since the urate is not degraded and utilised during negative nitrogen balance or during situations of high nitrogen demand such as oogenesis and moulting. Indeed it appears that herbivorous gecarcinid land crabs do not require a nitrogen store since they can meet their nitrogen requirements from a leaf litter diet. The location of the uricolytic enzymes in decapods suggests that the urate deposits may represent long-term storage of nitrogenous wastes. In isopods, the urate appears not to function as either a nitrogen store or storage excretion of nitrogenous wastes. In this group, it could act as a cation store during dehydration or as an antioxidant to prevent oxidative tissue damage. However, conditions which induce urate catabolism have yet to be conclusively demonstrated.
Stuart M. Linton; Jonathan C. Wright; Caitlin Howe. Nitrogenous Waste Metabolism Within Terrestrial Crustacea, with Special Reference to Purine Deposits and Their Metabolism. Acid-Base Balance and Nitrogen Excretion in Invertebrates 2016, 25 -59.
AMA StyleStuart M. Linton, Jonathan C. Wright, Caitlin Howe. Nitrogenous Waste Metabolism Within Terrestrial Crustacea, with Special Reference to Purine Deposits and Their Metabolism. Acid-Base Balance and Nitrogen Excretion in Invertebrates. 2016; ():25-59.
Chicago/Turabian StyleStuart M. Linton; Jonathan C. Wright; Caitlin Howe. 2016. "Nitrogenous Waste Metabolism Within Terrestrial Crustacea, with Special Reference to Purine Deposits and Their Metabolism." Acid-Base Balance and Nitrogen Excretion in Invertebrates , no. : 25-59.
Background: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation. Methods: We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs. Results: Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex (Pdiff < 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR < 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR < 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR = 0.80). Conclusions: OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs. Impact: This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261–9. ©2016 AACR.
Caitlin Howe; Xinhua Liu; Megan N. Hall; Vesna Ilievski; Marie A. Caudill; Olga Malysheva; Angela M. Lomax-Luu; Faruque Parvez; Abu B. Siddique; Hasan Shahriar; Mohammad N. Uddin; Tariqul Islam; Joseph H. Graziano; Max Costa; Mary V. Gamble. Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults. Cancer Epidemiology Biomarkers & Prevention 2016, 26, 261 -269.
AMA StyleCaitlin Howe, Xinhua Liu, Megan N. Hall, Vesna Ilievski, Marie A. Caudill, Olga Malysheva, Angela M. Lomax-Luu, Faruque Parvez, Abu B. Siddique, Hasan Shahriar, Mohammad N. Uddin, Tariqul Islam, Joseph H. Graziano, Max Costa, Mary V. Gamble. Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults. Cancer Epidemiology Biomarkers & Prevention. 2016; 26 (2):261-269.
Chicago/Turabian StyleCaitlin Howe; Xinhua Liu; Megan N. Hall; Vesna Ilievski; Marie A. Caudill; Olga Malysheva; Angela M. Lomax-Luu; Faruque Parvez; Abu B. Siddique; Hasan Shahriar; Mohammad N. Uddin; Tariqul Islam; Joseph H. Graziano; Max Costa; Mary V. Gamble. 2016. "Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults." Cancer Epidemiology Biomarkers & Prevention 26, no. 2: 261-269.
Exposure to inorganic arsenic is associated with numerous adverse health outcomes, with susceptibility differing by sex. Although evidence from in vitro studies suggests that arsenic alters post-translational histone modifications (PTHMs), evidence in humans is limited. The objectives were to determine: a) if arsenic exposure is associated with global (percent) levels of PTHMs H3K36me2, H3K36me3, and H3K79me2 in a sex-dependent manner, and b) if %PTHMs are stable when arsenic exposure is reduced. We examined associations between arsenic, measured in blood and urine, and %PTHMs in peripheral blood mononuclear cells from 317 participants enrolled in the Bangladesh Folic Acid and Creatine Trial (FACT). We also examined the stability of %PTHMs after the use of arsenic-removal water filters (n = 60). Associations between natural log-transformed (ln) urinary arsenic, adjusted for creatinine (uAsCr), and %H3K36me2 differed significantly between men and women (p = 0.01). ln(uAsCr) was positively associated with %H3K36me2 in men [β = 0.12; 95% confidence interval (CI): 0.01, 0.23, p = 0.03] but was negatively associated with %H3K36me2 in women (β = -0.05; 95% CI: -0.12, 0.02, p = 0.19). The patterns of associations with blood arsenic were similar. On average, water filter use was also associated with reductions in %H3K36me2 (p < 0.01), but this did not differ significantly by sex. Arsenic was not significantly associated with %H3K36me3 or %H3K79me2 in men or women. Arsenic exposure was associated with %H3K36me2 in a sex-specific manner but was not associated with %H3K36me3 or %H3K79me2. Additional studies are needed to assess changes in %H3K36me2 after arsenic removal. Howe CG, Liu X, Hall MN, Slavkovich V, Ilievski V, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Costa M, Gamble MV. 2016. Associations between blood and urine arsenic concentrations and global levels of post-translational histone modifications in Bangladeshi men and women. Environ Health Perspect 124:1234-1240; http://dx.doi.org/10.1289/ehp.1510412.
Caitlin Howe; Xinhua Liu; Megan N. Hall; Vesna Slavkovich; Vesna Ilievski; Faruque Parvez; Abu B. Siddique; Hasan Shahriar; Mohammad N. Uddin; Tariqul Islam; Joseph H. Graziano; Max Costa; Mary V. Gamble. Associations between Blood and Urine Arsenic Concentrations and Global Levels of Post-Translational Histone Modifications in Bangladeshi Men and Women. Environmental Health Perspectives 2016, 124, 1234 -1240.
AMA StyleCaitlin Howe, Xinhua Liu, Megan N. Hall, Vesna Slavkovich, Vesna Ilievski, Faruque Parvez, Abu B. Siddique, Hasan Shahriar, Mohammad N. Uddin, Tariqul Islam, Joseph H. Graziano, Max Costa, Mary V. Gamble. Associations between Blood and Urine Arsenic Concentrations and Global Levels of Post-Translational Histone Modifications in Bangladeshi Men and Women. Environmental Health Perspectives. 2016; 124 (8):1234-1240.
Chicago/Turabian StyleCaitlin Howe; Xinhua Liu; Megan N. Hall; Vesna Slavkovich; Vesna Ilievski; Faruque Parvez; Abu B. Siddique; Hasan Shahriar; Mohammad N. Uddin; Tariqul Islam; Joseph H. Graziano; Max Costa; Mary V. Gamble. 2016. "Associations between Blood and Urine Arsenic Concentrations and Global Levels of Post-Translational Histone Modifications in Bangladeshi Men and Women." Environmental Health Perspectives 124, no. 8: 1234-1240.