5,10-亚甲基四氢叶酸还原酶基因C677T位点突变与地方性砷中毒皮肤病变发生关系的研究

目的　 5 ,10- 亚甲基四氢叶酸还原酶 (MTHFR)是叶酸代谢关键酶 ,旨在了解该酶基因C6 77T位点突变是否是地方性砷中毒皮肤病变发生的遗传易感因素。方法　选择 5 0名出现砷性皮肤病变居民作为皮肤病变组 ,以同地区饮水砷浓度相近的 35名正常人作为对照 ,进行MTHFR基因C6 77T位点多态性分析(PCR- RFLP法 )、血清叶酸测定 (微生物法 )和维生素B1 2 测定 (电化学发光法 )。结果　皮肤病变组MTHFR基因C6 77T位点TT基因型占 34. 0 % ,T等位基因频率为 5 6 . 0 %。皮肤病变组和对照组基因型构成和等位基因频率差异无显著性。两组血清叶酸、VitB1 2 水平差异均无显著性。以血清叶酸水平≥ 10. 5nmol L且CC基因型作为参照 ,其它组粗OR值和经Logistic回归分析控制性别、年龄、水砷浓度、吸烟后的校正OR值均大于 1,但 95 %CI包含 1。结论　MTHFR基因C6 77T位点多态性与地方性砷中毒皮肤病变的发生无明显关联。

Study on the relationship between methylenetetra-hydrofolatereductase gene (677C→T) mutation and skin lesions in endemic arsenic poisoning

OBJECTIVE: Methylene tetrahydrofolate reductase (MTHFR) is the key enzyme in folate metabolism. We examined whether single nucleotide 677 C-->T mutation in the MTHFR gene could affect the occurrence of skin lesions in endemic arsenic poisoning. METHODS: Fifty individuals with arsenic-induced skin lesions were identified as cases, and 35 individuals without skin lesions from the same village were selected as controls. The MTHFR C677T polymorphism was analyzed by PCR-RFLP method, serum folic acid and Vitamin B12 were determined by microbiological assay and the electrochemiluminescence immunoassay, respectively. RESULTS: The frequencies of TT genotype and T allele in case group were 34.0% and 56.0%, respectively, and were not significantly different from those in controls. There was no significant difference between case and control group in the levels of folic acid and Vitamin B12 in serum. Compared to subjects carrying the CC genotype and having the level of folic acid above 10.5 nmol/L, other subjects were at elevated risk of skin lesions, but the 95% CI of both crude OR and adjusted OR (controlled for age, gender, smoking and arsenic level in drinking water) include 1. CONCLUSION: This study did not find the relationship between MTHFR gene (677C-->T) mutation and skin lesions in endemic arsenic poisoning.