Institute of Environmental Medicine, Unit of Metals and Health, Karolinska Institutet, Stockholm, Sweden.
International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
Toxicol Appl Pharmacol. 2018 Oct 15;357:80-87. doi: 10.1016/j.taap.2018.08.020. Epub 2018 Aug 25.
Arsenic methylation efficiency, a susceptibility factor for arsenic toxicity, is in adults partly explained by variation in arsenite methyltransferase (AS3MT) gene. Little is known about the role of AS3MT for children's arsenic methylation.
Evaluating associations between AS3MT polymorphisms and children's arsenic methylation efficiency.
Bangladeshi children's arsenic exposure (9-years; n = 424) was assessed as sum urinary concentration of inorganic arsenic (iAs) and its metabolites (monomethylarsonic acid [MMA] and dimethylarsinic acid [DMA]) using HPLC-HG-ICPMS. Arsenic methylation efficiency was assessed by the individual metabolite fractions (%). AS3MT polymorphisms (rs7085104, rs3740400, rs3740393 and rs1046778) were genotyped using TaqMan SNP genotyping assays.
We found higher %iAs and %MMA, and lower %DMA in urine, among rs1046778 TT carriers (median 8.8%, 9.6% and 81.1% for iAs, MMA and DMA, respectively), compared to CC carriers (median 7.0%, 8.3% and 84.9%). These associations were significant in multivariable-adjusted linear regression models: B-coefficients for TT vs CC were 1.26, 1.33 and -2.59 for iAs, MMA and DMA, respectively. Effect estimates were slightly stronger when restricting the analyses to children with urinary arsenic ≥58 μg/L (reducing the impact of ingested DMA). Estimates in girls were slightly stronger than in boys, although there were no significant differences between boys and girls. No clear associations were found for the other AS3MT polymorphisms.
One out of four AS3MT polymorphisms, previously associated with arsenic methylation in adults, was associated with arsenic methylation in children. Thus, AS3MT variation seems to influence arsenic methylation efficiency in children to a lesser extent than in adults.
砷甲基化效率是砷毒性的易感性因素之一，在成年人中，部分原因是亚砷酸甲基转移酶（AS3MT）基因的变异。关于 AS3MT 对儿童砷甲基化的作用知之甚少。
评估 AS3MT 多态性与儿童砷甲基化效率之间的关联。
使用 HPLC-HG-ICPMS 评估孟加拉国儿童（9 岁；n=424）的砷暴露情况，评估指标为尿液中无机砷（iAs）及其代谢物（一甲基砷酸 [MMA]和二甲基砷酸 [DMA]）的总和浓度。砷甲基化效率通过个体代谢物分数（%）进行评估。使用 TaqMan SNP 基因分型检测方法对 AS3MT 多态性（rs7085104、rs3740400、rs3740393 和 rs1046778）进行基因分型。
与 CC 携带者（中位数分别为 7.0%、8.3%和 84.9%）相比，rs1046778 TT 携带者的尿液中 iAs、MMA 和 DMA 的%值更高，而 DMA 的%值更低（中位数分别为 8.8%、9.6%和 81.1%）。这些关联在多变量调整的线性回归模型中具有统计学意义：TT 与 CC 相比，iAs、MMA 和 DMA 的 B 系数分别为 1.26、1.33 和-2.59。当将分析限制在尿液中砷含量≥58μg/L 的儿童时（减少摄入 DMA 的影响），估计值略高。女孩的估计值略高于男孩，尽管男孩和女孩之间没有显著差异。其他 AS3MT 多态性没有发现明显的关联。
先前与成人砷甲基化相关的 AS3MT 多态性之一与儿童砷甲基化相关。因此，与成人相比，AS3MT 变异对儿童砷甲基化效率的影响较小。
