Interactive Influence ofN6AMT1andAs3MTGenetic Variations on Arsenic Metabolism in the Population of Inner Mongolia, China

• DOI: 10.1093/toxsci/kfw181
• Publication Date: 2016-09-17T02:39:16Z
• Authors: Xushen Chen; Xiaojuan Guo; Ping He; Jing Nie; Xiaoyan Yan; Jinqiu Zhu; Luoping Zhang; Guangyun Mao; Hongmei Wu; Zhiyue Liu; Diana Aga; Peilin Xu; Martyn Smith; Xuefeng Ren
• Keywords: Inner mongolia; Arsenic toxicity; Chinese population

Chronic arsenic exposure via drinking water has become a worldwide public health concern. In humans, inorganic (iAs) is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic (DMA) mainly mediated by (+3 oxidation state) methyltransferase (As3MT). We reported recently that N-6 adenine-specific DNA 1 (N6AMT1) was involved in metabolism, examined its interactive effect with As3MT on metabolism vitro. To further evaluate the of N6AMT1 biomethylation we conducted human population-based study including 289 subjects living rural villages Inner Mongolia, China, assessed their urinary metabolites profiles relation genetic polymorphisms haplotypes As3MT. Five single nucleotide (SNPs; rs1003671, rs7282257, rs2065266, rs2738966, rs2248501) haplotype 2_GGCCAT were significantly associated percentage iAs (% iAs) urine (e.g., for mean 9.62% TT, 6.73% AA). Rs1003671 also significant relationship MMA DMA (the %MMA 24.95% GA, 31.69% GG; % 69.21% 59.82% GG). The combined 2_GCAC showed consistence additive significance each iAs: 5.47% 9.36% carriers both null haplotypes, respectively. Overall, Chinese population, interaction observed specific combinations.