Ⅰ、Ⅱ相代谢酶基因多态性与氯乙烯作业工人DNA损伤的关系研究  

Relationship between genetic polymorphisms of phase Ⅰ and phase Ⅱ metabolizing enzymes and DNA damage of workers exposed to vinyl chloride monomer

作　　者：冀芳[1] 朱守民[1] 孙品[1] 王威[1] 李俊[2] 柴尚健[2] 夏昭林[1] 

机构地区：[1]复旦大学公共卫生学院劳动卫生教研室公共卫生安全教育部重点实验室,上海200032 [2]上海氯碱化工股份有限公司

出　　处：《卫生研究》2009年第1期7-11,共5页Journal of Hygiene Research

基　　金：国家自然科学基金资助项目(No.30070650,30671740);国家973项目(2002CB512902);科技部支撑计划(No.2006BAK05B01-02)

摘　　要：目的探讨Ⅰ相、Ⅱ相代谢酶基因多态性与氯乙烯(VCM)作业工人外周血淋巴细胞DNA损伤的关系。方法应用彗星实验测定87名VCM作业工人外周血淋巴细胞DNA损伤情况,并采用病例-对照设计,按彗星发生率将工人分为DNA损伤组和对照组。用PCR-RFLP法测CYP2E1(rs3813867)基因多态;PCR法测GSTT1、GSTM1缺失情况;应用TaqManPCR分析技术判定GSTP1(rs947894)、CYP1A1(rs1048943,rs4646903)和UGT1A6(rs6759892,rs1105879,rs4124874,rs3755319,rs887829,rs4148323)基因型。结果经χ2检验,CYP2E1基因rs3813867c1c1和c1c2+c2c2基因型、GSTP1基因rs947894AA和AG+GG基因型及UGT1A6基因rs1105879AA和AC+CC基因型在DNA损伤组和对照组间的分布差异有显著性(分别为P=0.029,P=0.004和P=0.002)。多元Logistic回归分析的结果表明,携带GSTP1基因rs947894AG+GG基因型的个体较携带AA基因型个体DNA损伤的风险性升高(OR=13.393,95%CI:2.410～74.431,P<0.01);携带UGT1A6基因rs1105879AC+CC基因型的个体较携带AA基因型个体DNA损伤的风险性降低(OR=0.064,95%CI:0.006～0.637,P<0.05)。单倍型分析结果表明,UGT1A6基因TCCTAG单倍型在对照组的分布频率高于DNA损伤组(P<0.05)。结论携带GSTP1基因rs947894AG或GG基因型和UGT1A6基因rs1105879AA基因型的个体发生DNA损伤的风险增高,它们可能为氯乙烯致DNA损伤的易感人群。而UGT1A6基因TCCTAG单倍型对氯乙烯中毒可能具有保护作用。Objective To investigate the association between genetic polymorphisms in phase Ⅰ and phase Ⅱ metabolism genes and DNA damage in peripheral blood lymphocytes of workers exposed to vinyl chloride monomer (VCM).Methods 87 workers occupationally exposed to VCM were investigated. DNA damage in peripheral blood lymphocytes was measured by Comet Assay; the workers were divided into case,control groups based on the comet frequency. Genotypes of CYP2E1 (rs3813867) were identified by the PCR-RFLP,null genotypes of G...

关 键 词：氯乙烯 DNA损伤 代谢酶 基因多态性 

分 类 号：R131[医药卫生—劳动卫生]