Epigenetic marks change during fetal development, adult life, and aging. Some changes play an important role in the establishment and regulation of gene programs, but others seem to occur without any apparent physiological role. An important future challenge in the field of epigenetics will be to describe how the environment affects both of these types of epigenetic change and to learn if interaction between them can determine healthy and disease phenotypes during lifetime. Here we discuss how chemical and physical environmental stressors, diet, life habits, and pharmacological treatments can affect the epigenome during lifetime and the possible impact of these epigenetic changes on pathophysiological processes.

The purpose of this study was to determine the global patterns of aberrant DNA methylation in thyroid cancer. We have used DNA methylation arrays to determine, for the first time, the genome-wide promoter methylation status of papillary, follicular, medullary, and anaplastic thyroid tumors. We identified 262 and 352 hypermethylated and 13 and 21 hypomethylated genes in differentiated papillary and follicular tumors, respectively. Interestingly, the other tumor types analyzed displayed more hypomethylated genes (280 in anaplastic and 393 in medullary tumors) than aberrantly hypermethylated genes (86 in anaplastic and 131 in medullary tumors). Among the genes indentified, we show that 4 potential tumor suppressor genes (ADAMTS8, HOXB4, ZIC1, and KISS1R) and 4 potential oncogenes (INSL4, DPPA2, TCL1B, and NOTCH4) are frequently regulated by aberrant methylation in primary thyroid tumors. In addition, we show that aberrant promoter hypomethylation-associated overexpression of MAP17 might promote tumor growth in thyroid cancer. Thyroid cancer subtypes present differential promoter methylation signatures, and nondifferentiated subtypes are characterized by aberrant promoter hypomethylation rather than hypermethylation. Additional studies are needed to determine the potential clinical interest of the tumor subtype-specific DNA methylation signatures described herein and the role of aberrant promoter hypomethylation in nondifferentiated thyroid tumors.

The aim of the present study was to investigate, in 152 Spanish patients infected with hepatitis C virus (HCV), the possibility that killer cell immu

The role of MICA antibodies in acute heart allograft rejection was examined utilizing 190 pre‐ and post‐transplant serum samples from 44 patients collected during the first year after transplantation. MICA antibodies were detected by CDC test on recombinant cell lines and by the newly developed Luminex MICA antibody detection assay. Additionally, MICA expression was analyzed by ‘real time’ RT‐PCR and by immunohistochemistry in 10 endomyocardial biopsies. Only two subjects had HLA antibodies post‐transplant. Nevertheless, MICA antibodies were found in a significant number of subjects. The prevalence of MICA antibodies was significantly higher among those with severe acute rejection (AR) than in those without rejection (60.7% vs. 14.3%, p = 0.0038 by CDC; 55.5% vs. 5.7%, p = 0.0020 by Luminex). In most cases, the appearance of MICA antibodies post‐transplant precedes AR. Following transplantation, MICA up‐regulation correlated with histological evidence of severe rejection. Monitoring for MICA antibodies post‐transplant may be useful to establish new risk factors for acute rejection.

Objective To investigate the contribution of HLA class I alleles in the susceptibility to primary ankylosing spondylitis (AS) in West African patients living in Togo. Methods A large epidemiologic analysis of 9,065 West African rheumatology patients living in Togo was performed in order to identify those who had AS. Eight Togolese patients with AS were identified. HLA was typed by polymerase chain reaction using sequence‐specific oligonucleotide probes. DNA typing was also performed on a control population of 85 healthy subjects matched for ethnic background. Results A significant association between AS and B*14 was identified. This allele was found in 62.5% of the AS patients (odds ratio 69), but was carried by only 2% of the healthy controls. Analysis for B14 subtypes showed that B*1403 was the predominant allele in AS patients (odds ratio 171), and that this allele was absent in healthy controls. B27 was virtually absent, being observed in only 1 AS patient (B*2705). Conclusion HLA–B*1403 shows the B27 “supertype” motif and may exert an effect on AS susceptibility according to the arthritogenic peptide model. The association of B*1403 with AS has not previously been reported in either population.