High arsenic metabolic efficiency in AS3MT287Thr allele carriers
High arsenic metabolic efficiency in AS3MT287Thr allele carriers
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DOI：
10.1097/fpc.0b013e3282f7f46b
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发表时间：
2008-04-01
影响因子：
2.6
通讯作者：
Marcos, Ricardo
中科院分区：
文献类型：
--
作者：
Hernandez, Alba;Xamena, Noel;Marcos, Ricardo
目的流行病学资料表明砷代谢存在广泛的个体差异。最近有研究表明，砷（III）甲基转移酶（AS3MT）酶催化亚砷酸和单甲基拉森酸（MMA）的甲基化。因此，AS3MT基因的遗传变异至少可以部分解释砷暴露反应的个体间差异。在早期的研究中，我们已经证明了AS3MT Met(287)Thr （C/T）多态性影响了智利一组职业暴露于砷的男性（n=50）的尿砷谱。方法为证实Met287Thr多态性对砷代谢的影响，对207名智利铜工业工人进行基因分型和尿谱分析。结果证实Met287Thr多态性确实影响该人群的砷代谢。携带变异（(287)Thr）的人甲基化效率更高，尿中MMA排泄量比正常等位基因纯合子的人多4.63% (P=0.0007)， MMA排泄量比标准高2.98倍（P=0.01）。结论287Thr变异体个体砷甲基化增加；因此，这些参与者可能面临砷暴露的毒性和遗传毒性影响的风险增加。
Objectives Epidemiological data indicate the existence of wide interindividual differences in arsenic metabolism. It has recently been shown that arsenic(III)methyltransferase (AS3MT) enzyme catalyses the methylation of arsenite and monomethylarsonous acid (MMA). Thus, genetic variations in the AS3MT gene could explain, at least partly, the interindividual variation in the response to arsenic exposure. In an earlier study, we have demonstrated that the AS3MT Met(287)Thr (C/T) polymorphism affected the urinary arsenic profile in a Chilean group of men (n=50) occupationally exposed to arsenic.Methods To confirm, the influence of the Met287Thr polymorphism in the metabolism of arsenic, a total of 207 Chilean men working at the copper industry were genotyped and their urinary profiles determined.Results The results confirm that Met287Thr polymorphism does influence arsenic metabolism in this population. Those carriers of the variant ((287)Thr) had a higher methylation efficiency, excreting 4.63% more MMA in urine (P=0.0007) and presenting a 2.98 times higher odd of excreting levels of MMA over the standard (P=0.01 1) than the participants homozygous for the normal allele.Conclusion We can conclude that individuals with the 287Thr variant display increased arsenic methylation; thus, those participants might be at increased risk for the toxic and genotoxic effects of arsenic exposure.