CYP2D6和CYP2E1基因多态性与职业性慢性锰中毒的易感性  

Genetic polymorphism of CYP2D6、CYP2E1 and susceptibility to chronic occupational manganism poisoning

作　　者：贾强[1] 赛林霖[1] 单永乐[1] 侯强[1] 李斌[2] 郭启明[1] 

机构地区：[1]山东省职业卫生与职业病防治研究院毒理室,山东济南250002 [2]中国疾病预防控制中心职业卫生与中毒控制所,北京100050

出　　处：《中国职业医学》2010年第2期95-98,共4页China Occupational Medicine

基　　金：科技部科研院所社会公益研究专项(2005DE101439)

摘　　要：目的探讨CYP2D6和CYP2E1基因多态性与慢性锰接触工人神经毒性易感性的关联。方法采用巢式病例-对照研究的方法,对同一车间的电焊作业工人通过为期1年的健康监护,根据神经系统检查结果,确定63例有早期神经系统异常的工人作为病例组。根据个人资料对每1例病例进行3～5名对照的匹配,确定240例未见任何神经系统异常的工人为对照组。采用限制性片段聚合酶链反应(PCR-RFLP)技术检测CYP2D6酶基因的2938位C/T突变多态性和CYP2E1第6内含子7668位T/A突变产生DraⅠ酶切多态性及5’非编码区1019C/T基因突变产生PstⅠ酶切多态性。结果以各基因位点的野生型为参照,调整吸烟、饮酒、工龄、年龄和性别影响因素后,病例组CYP2D6基因突变型纯合子LL基因型和等位基因频率均低于对照组。具有LL突变的个体锰接触作业时受神经系统损伤的危险性与具有野生型纯合子WtWt的个体相比下降了79%(OR=0.21,95%CI=0.05～0.93,P=0.04)。病例组CYP2E1PstⅠ酶切位点突变型等位基因C2C2频率(22.2%)略高于对照组(15.0%),但差异无统计学意义(P>0.05),基因型分布差异亦无统计学意义(P>0.05)。CYP2E1DraⅠ酶切位点基因型分布和等位基因频率在病例组和对照组中差异亦无统计学意义(P>0.05)。结论携带CYP2D6LL基因型的个体对职业性慢性锰中毒产生的神经损伤不易感,CYP2D6酶基因的2938位C/T突变可能为职业性慢性锰接触致神经系统损害的保护因素之一。Objective To explore the association between gene polymorphism of CYP2D6,CYP2E1 and susceptibility to manganese-induced neurotoxicity.Methods A nested case-control study was conducted in welders of a workshop for one year.According to the neural findings,the studied subjects were divided to 63 cases and 240 controls.DNA was extracted from blood samples and genotyping was conducted for CYP2D6,CYP2E1 DraI and CYP2E1 PstI.PCR restriction fragment length polymorphism （PCR-RFLP） was used to detect the single nucleotide polymorphisms （SNP） of 2 938 position in CYP2D6,7 668 position in the sixth extron of CYP2E1 and 1019 position in 5’ flanking region of CYP2E1.Results Adjusted by exposure history,gender,age,smoking and drinking status,both the LL genotype and allele frequencies of CYP2D6 were significantly lower in the case group compared with the control.Individuals with the homozygote polymorphism （LL） of CYP2D6 had a 79% of risk decrease of central nerve damage compared with the wild-type （WtWt,OR=0.21,95% CI=0.05-0.93,P=0.04）.The allele and genotype frequency of CYP2E1 DraI and PstI were distributed similarly in the cases and controls（P0.05）.Conclusion The results suggest that the C/T mutation of 2 938 position in gene CYP2D6 might be a protective factor to manganese-induced central nerve damage.

关 键 词：锰中毒 CYP2D6 CYP2E1 基因多态性 神经毒性 

分 类 号：R135.1[医药卫生—劳动卫生]