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目的：探讨亚甲基四氢叶酸还原酶(MTHFR）基因SNP位点rs1801133(677 C>T）、5-甲基四氢叶酸高半胱氨酸甲基转移酶(MTR）基因SNP位点rs1805087(2756 A>G）多态性与地方性砷中毒易感性的关系。方法采用病例-对照研究方法,以内蒙古自治区地方性砷中毒病区140名出现砷性皮肤病变患者作为病例组,以同地区157名体检健康居民作为对照组,采集静脉血,乙二胺四乙酸二钠(EDTA）抗凝,采用聚合酶链反应-限制性片段长度多态性方法(PCR-PFLP法）,检测分析MTHFR 677 C>T位点和MTR 2756 A>G位点多态性。单因素Logistic回归分析年龄、性别、居住年限以及MTHFR 677 C>T、MTR 2756 A>G基因型对地方病砷中毒患病的影响。结果 MTHFR 677 C>T位点等位基因C出现频率在病例组和对照组分别为56.43%、52.55%,等位基因T出现频率分别为43.57%、47.45%,等位基因C、T出现频率两组比较差异无统计学意义(χ2=0.90, P>0.05）；MTR 2756 A>G位点等位基因A出现频率在病例组和对照组分别为93.93%、95.54%,等位基因G出现频率分别为6.07%、4.46%,等位基因A、G出现频率两组比较差异无统计学意义(χ2=0.84,P>0.05）。MTHFR 677 C>T位点CC基因型出现频率在病例组和对照组分别为22.86%、18.47%,CT基因型分别为67.14%、67.52%,TT基因型分别为10.00%、14.01%；将杂合型CT、突变型TT、杂合型CT和突变型TT合并与野生型CC比较差异无统计学意义(χ2=0.56、0.81、0.87,P均>0.05）。 MTR 2756 A>G位点AA基因型出现频率在病例组和对照组分别为87.86%、91.72%,AG基因型分别为12.14%、7.64%,GG基因型分别为0.00%、0.64%；将杂合型AG、突变型GG、杂合型AG和突变型GG合并与野生型AA比较差异无统计学意义(χ2=1.65、1.35、1.22,P均>0.05）。单因素Logistic回归分析显示,≥60岁组患地方性砷中毒的危险性是≤40岁组的2.78倍,居住年限≥40年患地方性砷中毒的危险性是居住年限0.05）。MTHFR 677 C>T杂合型CT、突变型TT分别与野生型CC患病率比较,差异无统计学意义(OR =1.53、1.63, P均>0.05）；MTR 2756 A>G杂合型AG、突变型GG分别与野生型AA患病率比较,差异无统计学意义(OR =1.04、1.20,P均>0.05）。结论研究人群样本中MTHFR 677 C>T位点和MTR 2756 A>G位点多态性与地方性砷中毒的易感性不存在相关关系。“,”Objective To investigate the relationship be tween 5, 10-methylenetetrahydrofolate reductase (MTHFR) SNP rs1801133 (677 C>T), 5-methytetrahydrofolate homocysteine s-methltransferase (MTR) SNP rs1805087 (2756 A>G) gene polymorphisms and susceptibility to endemic arsenic poisoning. Methods Case-control study design was employed to study 140 individuals who were identified as cases with arsenic induced skin lesions, and 157 individuals without skin lesions from the same villages were selected as controls in Inner Mongolia Autonomous Region, venous blood samples were collected, ethylenediamine tetraacetic acid disodium salt (EDTA) anticoagulant was added, MTHFR 677 C>T and MTR 2756 A>G genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-PFLP). Binary logistic analysis was used to analyze the affect of age, gender, period of residence, MTHFR 677 C>T and MTR 2756 A>G to endemic arsenicosis. Results MTHFR 677 C>T allele frequencies of C in case group and control group were 56.43% and 52.55%, respectively, and allele frequencies of T were 43.57% and 47.57%, respectively, the allele frequency between the two groups was not significantly different (χ2=0.90, P>0.05);MTR 2756 A>G allele frequencies of A in case group and control group were 93.93%and 95.54%, respectively, and allele frequencies of G were 6.07% and 4.46%, respectively, the allele frequency between the two groups was not significantly different (χ2= 0.84, P> 0.05). In MTHFR 677 C>T, CC genetypes in case group and control group were 22.86% and 18.47%, respectively; CT genotypes were 67.14% and 67.52%, respectively;TT genotypes were 10.00%and 14.01%, respectively. The differences between hybrid type CT, mutant TT, combined hybrid type CT with mutant TT and wild type CC were not significantly different (χ2=0.56, 0.81, 0.87, all P > 0.05). In MTR 2756 A>G, AA genetypes in case group and control group were 87.86% and 91.72, respectively;AG genotypes were 12.14%and 7.64%, GG genotypes were 0.00%and 0.64%, respectively. The differences between hybrid type AG, mutant type GG, combined hybrid type AG with mutant GG and wild type AA were not significantly different (χ2=1.65, 1.35, 1.22, all P> 0.05). The group of over 60 years old had higher risk of endemic arsenic poisoning with 2.78 times higher than the group of less 40 years old, the group of over 40 years old had higher risk of endemic arsenic poisoning with 1.85 times higher than the group of less than 40 years, and the difference was significant [odd ratio (OR) = 2.78, 1.85, P〈 0.01 or 〈 0.05]. There was no significant difference between the prevalence of men and women (OR =1.56, P>0.05). There was no significant difference in prevalence between wild type CC and hybrid type CT, mutation type TT in MTHFR 677 C>T, respectively (OR =1.53, 1.63, all P> 0.05). There was no significant difference in prevalence between wild type AA and hybrid type AG, mutation type GG in MTR 2756 A>G, respectively (OR = 1.53, 1.63, all P> 0.05). Conclusion This study does not find a positive correlation between MTHFR 677 C>T and MTR 2756 A>G polymorphism in endemic arsenicosis.