Introducción: FTO (Fat Mass and Obesity-related) se ha relacionado de manera consistente con la obesidad. Recientemente, Polimorfismos de Nucleótido Único (SNP) en este gen se han relacionado con el gen IRX3. Objetivo: Probar la hipótesis de que: i) SNPs en FTO e IRX3 están asociados con la obesidad y trastornos relacionados; ii) existe desequilibrio de ligamiento (LD) significativo entre ambos genes. Métodos: Se realizó un estudio transversal en la costa caribe colombiana. Se valoraron variables antropométricas y bioquímicas, la obesidad y trastornos metabólicos. Se genotipificaron 4 SNPs: 3 en FTO (rs17817449, rs8050136, rs9939609) y uno en IRX3 (rs3751723). Se estimó el LD entre estos SNPs. Se aplicó un modelo de regresión logística para estimar asociaciones. Resultados: Se incluyeron 792 sujetos. FTO e IRX3 no se encontraron en LD (D' ≤0.03; R2 ≤0.03). El genotipo TT (rs9939609) se encontró asociado con la circunferencia de la cintura (p= 0.04; adj-p= 0.01), y el SNP IRX3 con el Exceso de Peso (EP) (OR= 1.06, adj-p= 0.03). Se encontró un haplotipo FTO-IRX3 asociado con EP (G-A-A-T, rs17817449-rs8050136-rs9939609-rs3751723; OR= 0.67, p= 0.04). Esta asociación persistió después del ajuste para una población mixta (p= 0.03). Conclusiones: FTO se encontró asociado con la circunferencia de la cintura e IRX3 con EP en adultos latinoamericanos. Estas asociaciones persistieron tras el ajuste por sexo, edad y ascendencia genética. Aunque estos genes no estaban en LD, los hallazgos de un haplotipo entre FTO-IRX3 sugieren una interacción gen-gen asociada con un mayor riesgo de EP. Background: Fat Mass and Obesity-related (FTO) has been one of the genes consistently related to common obesity. Single nucleotide polymorphisms (SNPs) in FTO have been linked with the IRX3 gene. Aim: This study was designed by testing the hypothesis that: i) common SNPs in FTO and IRX3 are associated with obesity and related disorders; ii) there is significant linkage disequilibrium between both genes. Methods: A cross-sectional study was carried out on the Colombian Caribbean Coast. Anthropometric and biochemical variables were measured, and obesity and metabolic disorders were diagnosed. Four SNPs were genotyped: 3 at FTO locus (rs17817449, rs8050136, rs9939609) and one at IRX3 locus (rs3751723). LD between these SNPs was estimated. A logistic regression model was applied to estimate associations. Results: A total of 792 subjects were included. FTO and IRX3 were not in LD (D’≤ 0.03; R2≤ 0.03). TT genotype (rs9939609) was found to be associated with waist circumference (p= 0.04; adj-p=0.01), and IRX3 SNP with Body Weight Excess (BWE) (OR= 1.06, adj-p= 0.03). One FTO-IRX3 haplotype was associated with BWE (G-A-A-T, rs17817449-rs8050136-rs9939609-rs3751723; OR= 0.67, p= 0.04). The statistical significance of these relations continued after admixture adjustment for a three-hybrid population (p= 0.03). Conclusions: FTO was related to waist circumference, and IRX3 was associated with BWE in Latin American adults. This relation remained statistically significant after performing an adjustment for sex, age, and genetic ancestry. Despite these genes not being in LD, findings of a haplotype involving FTO-IRX3 suggest a gene-gene interaction associated with an increased risk of BWE.

Cardiovascular disease (CVD), the leading cause of global mortality, is intrinsically linked to atherosclerosis. Recent research suggests that respiratory function may be associated with the development of atherosclerosis. Alterations in the composition of the respiratory microbiome can negatively affect pulmonary function, which in turn may impact cardiovascular health through mechanisms that remain incompletely understood. To analyze the upper airway microbiome abundance and diversity in adults with subclinical atherosclerosis. A case–control study was conducted for atherosclerosis. Oropharyngeal swab samples were collected from participants in the CaRes cohort, for whom carotid Doppler, spirometry, blood chemistry, and clinical history data were available. Sequencing of the 16S ribosomal RNA gene was performed, followed by comparative analyses between subjects with and without atherosclerosis. A total of 100 subjects were analyzed (50 cases and 50 controls). The phylum Bacteroidetes was the most prevalent in both groups, followed by Firmicutes and Proteobacteria. Family Enterobacteriaceae was more abundant among case group, which included species such as Serratia, Klebsiella spp., and Campylobacter. Evaluation of alpha diversity indices revealed lower levels for cases group, with a Shannon diversity index of 2.61 compared to 4.07 in controls (p = 0.006). Differences in microbiota composition were observed between cases and controls. Specifically, the family Enterobacteriaceae was associated with the presence of atherosclerosis, suggesting its potential involvement in the progression of cardiovascular disease.

Subclinical atherosclerosis (SCA) has been associated with lung function in many populations. Accordingly, those factors involved in respiratory health may contribute to the mechanisms linking pulmonary and cardiovascular disorders. Since the airway microbiome plays a key role in respiratory pathophysiology, microbial abundance and diversity in the upper airway may be associated with SCA risk. This study aimed to assess the association of upper airway microbiome abundance and diversity with SCA risk. A nested case–control study was carried out among adults from the Southern Caribbean. SCA was defined by carotid Doppler ultrasound as a carotid intima-media thickness ≥ 0.8 mm or the presence of carotid plaque. Oropharyngeal mucosal samples were collected under fasting conditions, and the V3-V4 region of the 16SRNA gene was sequenced. Differences in genus-level abundance were assessed using Microbiome Multivariable Association with Linear Models 2 (MaAsLin2). Alpha-diversity indices were compared through Wilcoxon tests. Principal coordinates analysis (PCoA) and Permutational Multivariate Analysis of Variance (PERMANOVA), adjusted for age, body mass index, and smoking status, were performed to assess associations between Bray–Curtis distances and SCA. MaAsLin2 was also applied to determine predicted metabolic pathway enrichment. A total of 40 cases and 40 controls were analyzed. The oropharyngeal microbiomes composition was dominated by three genera: Prevotella (cases: 26.0%; controls: 29.8%), Veillonella (cases: 16.3%; controls: 13.7%) and Fusobacterium (cases: 7.5%; controls: 8.0%). Significant differences in relative abundance were found for Streptococcus, Aureimonas, Mogibaecterium, Candidatus Saccharimonas, Pseudomonas, Segatella, Stomatobaculum, Oribacterium and Lachnoanaerobaculum, with lower abundance in cases for all these genera. Alpha-diversity was lower in cases than in controls, as reflected by the Shannon index (cases: 5.95 IQR [4.87; 6.35] vs. controls: 6.49 IQR [6.29; 6.75], p < 0.001), Simpson index (cases: 0.994, IQR [0.989; 0.996] vs. controls: 0.997 IQR [0.997; 0.998], p < 0.001) and Chao1 richness (cases: 1076.2 IQR [345.2; 1473.4] vs. controls: 1136.1, IQR [841.1; 1635.3], p = 0.04) were compared. In adjusted-PERMANOVA, 8.2% of microbiome variations were associated with SCA (pseudo-F = 7.49, R² = 0.082, p < 0.001), although this finding may have been influenced by intra-group dispersion among cases (PERMDISP: pseudo-F = 5.62, p = 0.018; Tukey’s HSD test: mean difference = −0.071, 95% CI [−0.118, −0.025], p = 0.003) Predicted enrichment of phenylalanine metabolism and indole alkaloid biosynthesis was higher in cases. In conclusion, these exploratory analyses suggest that reduced oropharyngeal microbiome diversity is associated with SCA. Further studies are warranted to clarify the role of the airway microbiome on cardiovascular outcomes.