三价砷甲基转移酶基因多态性与地方性砷中毒易感性的关系研究  

Relationship between arsenic（＋3 oxidation state） methyltransferase genetic polymorphisms and susceptibility to endemic arsenism

作　　者：侯文胜 张丽芳 裴秋玲[2] 

机构地区：[1]中国石油集团石油职业卫生技术服务中心中心实验室,廊坊065000 [2]山西医科大学公共卫生学院毒理学教研室

出　　处：《中华地方病学杂志》2013年第1期33-37,共5页Chinese Journal of Endemiology

基　　金：山西省自然科学基金（20051094）;山西省回国人员基金（200527）;山西省科技攻关项目（2006031087-11）

摘　　要：目的探讨砷代谢相关酶三价砷甲基转移酶[arsenic（＋3oxidationstate）methyltransferase，AS3MT]单核苷酸多态性与地方性砷中毒患病风险的关系。方法采用聚合酶链反应一限制性酶切片段多态性一单链构象多态性（PCR—RFLP—SSCP）技术对79名砷中毒患者和110名正常健康人群外周血中AS3MT基因第8内含子和第9外显子的突变情况进行初筛，并进一步对异常带型进行直接DNA测序，以确定突变位点及类型。对AS3MT基因多态性进行单因素分析和多因素非条件Logistic回归分析。结果病例组AS3MT基因第8内含子上9149位碱基（AS3MT_9149）A—C突变的发生率（19．O％，15／79）低于对照组（23．6％，26／110），病例组AS3MT基因第9外显子上287位密码子（AS3MT-287）ATG—AC／TG突变的发生率（10．1％，8／79）低于对照组（11．8％，13／110），但差异均无统计学意义（P均〉0．05）。在多因素分析中调整年龄、性别等因素后，AS3MT基因多态性与地方性砷中毒发病仍无统计学意义[AS3MT-9149：比值比（OR）=0．59，95％可信区间（C／）为O．26—1．31，P=0．195；AS3Mn287：OR=0．85，95％C／为0．32—2．30，P=0．751]。结论AS3MT-9149和AS3MT-287多态性与地方性砷中毒易感性无显著关系。出现这种情况的原因可能与分析的样本量较小，或者是有关的多态性位点在AS3MT基因其他的外显子或非编码区上有关。Objective To investigate the association between arsenic（＋3 oxidation state） methyltransferase （AS3MT） genetic polymorphism and susceptibility to endemic arsenism. Methods Polymerase chain reaction- restriction fragment length polymorphism-single strand conformation polymorphism（PCR-RFLP-SSCP） technology was performed to detect mutations of AS3MT gene intron 8 and exon 9 in genome DNA of the 79 cases and 110 controls. PCR products with abnormal band forms were further sequenced to find the types and sites of mutation. Chi-square test and multivariate Logistic analyses were conducted. Results The incidence of the 9149 base mutation （A→ C） in AS3MT gene intron 8（AS3MT-9149） in case group（19.0%, 15/79） was lower than that in control group （ 23.6%, 26/110）. The incidence of the codon 287 mutation （ATG→AT/CG） in AS3MT gene exon 9 （ AS3MT-287 ） in case group（10.1%, 8/79） was lower than that in control group （11.8%, 13/110）. However, statistical analysis indicated no significant difference in both mutations between two groups [ AS3MT-9149： odds ratio （OR） = 0.59, 95% confidence interval（C/） ： 0.26 - 1.31, P = 0.195 ; AS3MT-287 ： OR = 0.85, 95% CI： 0.32 - 2.30, P= 0.751 ]. Conclusions There are no significant association between the genetic polymorphisms of AS3MT-9149, AS3MT- 287 and the susceptibility to endemic arsenism. Similarly, due to small sample amount, we can not exclude the possibility that these gene polymorphisms are related to susceptibility to endemic arsenism.

关 键 词：砷中毒 三价砷甲基转移酶 聚合酶链反应 基因 多态性 限制性片段长度 

分 类 号：R599[医药卫生—内科学]