Associations between Blood and Urine Arsenic Concentrations and Global Levels of Post-Translational Histone Modifications in Bangladeshi Men and Women.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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). RESULTS: Associations between natural log-transformed (ln) urinary arsenic, adjusted for creatinine (uAs(Cr)), and % H3K36me2 differed significantly between men and women (p = 0.01). ln(uAs(Cr)) was positively associated with % H3K36me2 in men [beta = 0.12; 95% confidence interval (CI): 0.01, 0.23, p = 0.03] but was negatively associated with % H3K36me2 in women (beta = -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. CONCLUSIONS: 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.