5,10-亚甲基四氢叶酸还酶基因多态性与砷甲基化代谢的关系

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0.05 mg/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);MTHFR C677T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.

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

Objective:To study the relationship between 5,10-methylenetetrahydrofolate reductase(MTHFR)genetic polymorphism and arsenic metabolism and the role of folate in it.Methods:Forty-three 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 As3 (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.