Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults

摘要: Background: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs also influenced nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation. Methods: We measured global levels of three PTHMs, dysregulated cancers (H3K36me2, H3K36me3, H3K79me2), peripheral blood mononuclear cells (PBMCs) from 324 participants enrolled the Folic Acid and Creatine Trial, a randomized trial arsenic-exposed Bangladeshi adults. Sex-specific associations between several OCM indices (folate, vitamin B12, choline, betaine, homocysteine) were examined at baseline using regression models, adjusted for multiple tests controlling false discovery rate (PFDR). evaluated effects FA supplementation (400 µg/day 12 weeks), compared with placebo, on PTHMs. Results: Associations choline H3K36me2 B12 H3K79me2, differed significantly sex (Pdiff < 0.01 0.05, respectively). Among men, plasma was positively associated (PFDR 0.05), among women, H3K79me2 0.01). did not alter any = 0.80). Conclusions: influence sex-dependent manner, supplementation, this dose duration, does PBMCs. Impact: This is first study to examine influences population that have increased susceptibility cancer development due widespread exposure arsenic-contaminated drinking water high prevalence hyperhomocysteinemia.