Objective To study the association of the gene polymorphism of arsenic (+3 oxidation state) methyltransferase (As3MT) and N-6-adenine-specific DNA methyltransferase 1 (N6AMT1) with arsenic-induced skin lesions (AISL), and explore the interaction between gene polymorphism of As3MT/N6AMT1 and environment factors.
Methods From September 2010 to December 2011, we conducted a survey among 335 adult residents (mean age: 50.59 ± 11.24) in 3 arsenic exposed villages stratified and randomly selected, based on the results of average arsenic concentration tests in previous years in Wuyuan county of Inner Mongolia Autonomous Region; then 65 residents diagnosed with AISL were assigned into a case group and the others into a control group. Blood samples were collected among all the participants for genotype detections of As3MT and N6AMT1 genes with MassARRAY® molecular weight array platform. Urinary arsenic profiles of the participants were determined with high-performance liquid chromatography/inductively coupled plasma-mass spectrometry. The durations of arsenic exposure of the participants were determined according to their use time of high-arsenic drinking water. Multifactoral dimensionality reduction and multivariate ridge regression model were adoopted to assess gene-environment interactive effects on AISL.
Results The CA/AA genotype of As3MT rs3740400, the GC/CC genotype of N6AMT1 rs1006903 and the elevated urinary dimethylarsinic acid (DMA) level were significant independent risk factors of AISL (P < 0.05 for all). Significant association of the interaction between As3MT rs3740400 genotype and urinary inorganic arsenic (iAs)-monomethylarsonic acid (MMA) with the risk of AISL (odds ratio = 0.62, 95% confidence interval: 0.41, 0.94; P = 0.024) was observed, with the accuracy rate of 0.5776 and a cross-validation consistency of 9/10 for the established 3 factors analysis model.
Conclusion Genetic variants in As3MT and N6AMT1 genes and urine DMA level are independently associated with AISL. The interaction among As3MT rs3740400 gene, urinary iAs, and MMA level plays an important role in the development of arsenicalism in the population with chronic arsenic exposure through drinking water.
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