5,10-亚甲基四氢叶酸还原酶基因多态性与砷甲基化代谢的关系

Relationship between 5,10-methylenetetrahydrofolate reductase genetic polymorphism and arsenic metabolism

目的:探讨5,10-亚甲基四氢叶酸还原酶(5,10-methylenetetrahydrofolate reductase,MTHFR)基因多态性及其与叶酸联合作用对砷甲基化代谢的影响。方法:在砷中毒流行区选择饮水史清楚、饮水砷含量高于0.05mg/L的43名居民,采集空腹静脉血并收集晨尿,以聚合酶链反应-限制性长度多态性方法分析MTHFR基因C677T位点多态性,采用高效液相色谱-氢化物发生-原子荧光法检测尿中各种形态的砷,采用微生物法测定血清中叶酸水平。比较不同MTHFR基因型及其和叶酸联合作用与尿中砷化物百分构成的关系。结果:和MTHFR原型基因个体相比,MTHFR基因677位突变个体(包括杂合突变和纯合突变)尿中As3+构成增加(r=27.17,P=0.029),而二甲基胂酸百分含量下降(r=26.57,P=0.033);MTHFRC677T基因型和叶酸联合作用未对尿中不同砷化物百分构成产生影响(P>0.05)。结论:MTHFR基因C677T位点多态性可能影响个体砷代谢能力,且这种作用独立于血清叶酸水平。

Objective： To study the relationship between 5,10-methylenetetrahydrofolate reductase （MTHFR） genetic polymorphism and arsenic metabolism and the role of folate in it. Methods： Fortythree indiviuals who were exposed to arsenic more than 0.05mg/L in well water were chosen and the vein blood and morning urine was collected; The MTHFR C677 polymorphism was analyzed by PCR-RFLP method ; Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic fluorescence spectrometry; Microbiological assay was used to estimate serum folate. Results： Subjects with the genotype of CT/TT had the increased percentage of urinary As^3＋（ r = 27. 17, P = 0. 029 ） and decreased percentage of urinary dimethylarsinic acid （ r = 26.57, P = 0.033）. No association was observed among serum folate, genetic polymorphisms of MTHFR C677 and the percentage of urinary arsenic （ P 〉 0.05 ）. Conclusion： Genetic polymorphism of MTHFR C677 was signifcantly associated with arsenic methylation and this effect was not associated with the serum folate.