title: Interactive Influence of N6AMT1 and As3MT Genetic Variations on Arsenic Metabolism in the Population of Inner Mongolia, China.
abstract: Chronic arsenic exposure via drinking water has become a worldwide public health concern. In humans, inorganic arsenic (iAs) is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) mainly mediated by arsenic (+3 oxidation state) methyltransferase (As3MT). We reported recently that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) was involved in arsenic metabolism, and examined its interactive effect with As3MT on arsenic metabolism in vitro To further evaluate the interactive effect of N6AMT1 and As3MT on arsenic biomethylation in humans, we conducted a human population-based study including 289 subjects living in rural villages in Inner Mongolia, China, and assessed their urinary arsenic metabolites profiles in relation to genetic polymorphisms and haplotypes of N6AMT1 and As3MT Five N6AMT1 single nucleotide polymorphisms (SNPs; rs1003671, rs7282257, rs2065266, rs2738966, rs2248501) and the N6AMT1 haplotype 2_GGCCAT were significantly associated with the percentage of iAs (% iAs) in urine (e.g., for rs7282257, mean was 9.62% for TT, 6.73% for AA). Rs1003671 was also in a significant relationship with urinary MMA and DMA (the mean of %MMA was 24.95% for GA, 31.69% for GG; the mean of % DMA was 69.21% for GA, 59.82% for GG). The combined effect of N6AMT1 haplotype 2_GGCCAT and As3MT haplotype 2_GCAC showed consistence with the additive significance of each haplotype on % iAs: the mean was 5.47% and 9.36% for carriers with both and null haplotypes, respectively. Overall, we showed that N6AMT1 genetic polymorphisms were associated with arsenic biomethylation in the Chinese population, and its interaction with As3MT was observed in specific haplotype combinations.
authors.affiliation: The Key Laboratory of Gene Engineering of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.|Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, 14214.
authors.forename: Xushen
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Public and Environmental Health, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.|Inner Mongolia Medical University, Hohhot 010110, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Chemistry, University at Buffalo, Buffalo, New York, 14260.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, 14214.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, 14214.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, 14214.
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Zhu
authors.affiliation: School of Public Health, University of California at Berkeley, Berkeley, California, 94720.
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Public and Environmental Health, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
authors.forename: Guangyun
authors.initials: G
authors.lastname: Mao
authors.affiliation: School of Public and Environmental Health, Wenzhou Medical University, Wenzhou 325035, People's Republic of China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Inner Mongolia Medical University, Hohhot 010110, People's Republic of China.
authors.forename: Zhiyue
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Chemistry, University at Buffalo, Buffalo, New York, 14260.
authors.forename: Diana
authors.initials: D
authors.lastname: Aga
authors.affiliation: The Key Laboratory of Gene Engineering of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
authors.forename: Peilin
authors.initials: P
authors.lastname: Xu
authors.affiliation: School of Public Health, University of California at Berkeley, Berkeley, California, 94720.
authors.forename: Martyn
authors.initials: M
authors.lastname: Smith
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, 14214 xuefengr@buffalo.edu.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Ren
mesh_terms: D000328:Adult; D001151:Arsenic / Q000378:metabolism*; D002681:China; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics*
chemical_list: D008780:Methyltransferases; C505756:AS3MT protein, human; C000607900:N6AMT1 protein, human; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D001151:Arsenic
keywords: As3MT; N6AMT1; arsenic metabolism; haplotype.; polymorphism