p16基因甲基化与地方性砷中毒发病关系的条件logistic回归分析

Conditional logistic regression analysis of the relationship between methylation of p16 gene and endemic arsenism

目的探索p16基因甲基化与地方性砷中毒(地砷病)发病的关系。方法以病区对照和非病区对照进行两项1∶1配对病例对照观察,病例组选自病区确诊地砷病患者共40例,对照组分别选自病区与非病区的非患者和正常人,进行年龄、性别匹配。采用甲基化特异性PCR(MS鄄PCR)技术,测定病区人群血标本p16基因甲基化水平,并用条件logistic回归分析方法处理资料。结果病例与病区对照分析结果表明p16甲基化(P=0.1343)对地砷病发病的影响无显著意义;而饮水砷(P=0.0039)和饮水年限(P=0.0154)对地砷病发病的影响有显著意义。病例与非病区对照分析结果表明p16甲基化(P=0.0019)对地砷病发病的影响有极显著意义。结论p16基因甲基化与地砷病发病可能存在病因联系。

Objective To determine the relationship between methylation of p16 gene and occurrence of endemic arsenicism. Methods Two 1∶ 1 pair-matched case-control studies were conducted. Cases were 40 typical and definitely diagnosed patients with endemic arsenism, selected from the areas prevalent with it. Forty controls were selected from the areas prevalent and non-prevalent with endemic arsenism, respectively, matched on age and sex. Methylation of p16 gene in the blood specimens were analyzed for all the subjects with MS-PCR techniques. Risk factors for endemic arsenism were analyzed with conditional logistic regression model. Results Analysis for cases and controls from the areas prevalent with endemic arsenism showed that hypermethylation of p16 gene(P = 0.134 3) was not significantly associated with the prevalence of endemic arsenism, while both concentration of arsenic in the drinking water (P = 0.003 9) and years to drink the water(P = 0.015 4) were significantly associated with the prevalence of endemic arsenism. Analysis for the cases and controls from the areas non-prevalent with endemic arsenism indicated that hypermethylation of p16 gene (P = 0.001 9) was significantly associated with the prevalence of endemic arsenism. Conclusions Hypermethylation of p16 gene in the blood specimens might serve an etiological factor for endemic arsenism.