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魏亚萍, 侯祥庆, 蓝园, 左菁菁, 李举双, 王涛, 毛广运. As3MT、N6AMT1基因-环境交互作用对砷暴露所致皮肤损伤影响[J]. 中国公共卫生, 2019, 35(2): 188-192. DOI: 10.11847/zgggws1120894
引用本文: 魏亚萍, 侯祥庆, 蓝园, 左菁菁, 李举双, 王涛, 毛广运. As3MT、N6AMT1基因-环境交互作用对砷暴露所致皮肤损伤影响[J]. 中国公共卫生, 2019, 35(2): 188-192. DOI: 10.11847/zgggws1120894
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Ya-ping WEI, Xiang-qing HOU, Yuan LAN, . Gene-environment interaction effects of As3MT and N6AMT1 on arsenic-induced skin lesions[J]. Chinese Journal of Public Health, 2019, 35(2): 188-192. DOI: 10.11847/zgggws1120894
Citation: Ya-ping WEI, Xiang-qing HOU, Yuan LAN, . Gene-environment interaction effects of As3MT and N6AMT1 on arsenic-induced skin lesions[J]. Chinese Journal of Public Health, 2019, 35(2): 188-192. DOI: 10.11847/zgggws1120894
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As3MT、N6AMT1基因-环境交互作用对砷暴露所致皮肤损伤影响

Gene-environment interaction effects of As3MT and N6AMT1 on arsenic-induced skin lesions

    摘要
  • 摘要:
      目的  探讨砷甲基转移酶（As3MT）和N – 6 – 腺嘌呤特异性DNA甲基转移酶1（N6AMT1）基因多态性及基因 – 环境交互作用与砷暴露所致皮肤损伤（AISL）的关联性。
      方法  于2010年9月到2011年12月在内蒙古五原县入选饮水型砷暴露人群335人，65例被确诊患有AISL。应用MassARRAY®分子量阵列平台检测基因型，高效液相色谱 – 电感耦合等离子体质谱联用法测定尿砷代谢物，砷暴露时间由其高砷水饮用时间确定，多因子降维法与岭回归模型分析基因型、环境因素的单独效应及基因 – 环境的交互作用。
      结果  As3MT基因rs3740400位点CA/AA基因型、N6AMT1基因rs1006903位点GC/CC基因型和尿二甲基胂酸（DMA）升高为AISL的独立危险因素（P < 0.05）。rs3740400位点基因型 – 尿无机砷（iAs） – 单甲基胂酸（MMA）的交互作用与AISL发生风险间存在显著的统计学关联（OR = 0.62，95 % CI = 0.41～0.94，P = 0.024），模型的验证样本准确率为0.577 6，交叉验证一致性为9/10。
      结论  As3MT、N6AMT1基因多态性及尿砷化合物水平均与AISL独立相关，rs3740400位点基因型、尿iAs和MMA的交互作用在慢性砷中毒的发生发展中具有重要作用。

     

    Abstract:
      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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