毒物代谢酶的基因多态性与慢性苯中毒易感性  

Genetic polymorphisms involved in toxicant-metabolizing enzymes and susceptibility to benzene poisoning

作　　者：陈艳[1] 李桂兰[2] 许建宁[2] 吴春玲[2] 

机构地区：[1]新疆医科大学公共卫生学院卫生毒理学教研室,新疆乌鲁木齐830054 [2]中国疾病预防控制中心职业卫生与中毒控制所

出　　处：《毒理学杂志》2007年第1期11-15,共5页Journal of Toxicology

基　　金：国家自然科学基金资助项目(39870685)

摘　　要：目的探讨毒物代谢酶CYP2E1、MPO、NQOZ、GSTT1和GSTM1基因多态性与慢性苯中毒遗传易感性之间的关系。方法选择100名慢性苯中毒工人为病例组及90名同期接苯但无苯中毒表现的同工种工人为对照组，应用PCR-RFLP及多重PER方法判定CYP2E1、MPO、NQO1、GSTT1和GSTM1基因基因型。结果携带NQO1 C609T T/T基因型（纯合突变型）个体发生苯中毒的危险性是具有C／T基因型（杂合型）和C／C基因型（野生型）个体的2．82倍（95％CI：1．42—5．58，P〈0．05），是具有C/C基因型（野生型）个体的2．94倍（95％CI：1．25—6．90，P〈0．05）；携带GSTT1缺失型（null）基因型个体发生苯中毒的危险性是具GSIT1非缺失型（non-null）基因型个体的1．91倍（95％CI：1．05．3．45，P〈0．05）。未发现CYP2E1、MPO、GSTM1基因型与苯中毒之间的关系。同时携带NQO1 C609T纯合突变型（T／T）、GSTT1缺失型（null）与GSTM1缺失型（null）个体接苯时发生苯中毒的危险性最高，是NQO1 C609T杂合型（C／T）和野生型（C／C）、GSTT1非缺失型（non-null）与GSTM1非缺失型（non-null）个体的20．41倍（95％CI：3．79．111．11，P〈0．01）。结论基因之间的交互作用在苯中毒的发生中起重要作用。同时携带NQO1 C609T纯合突变基因型（T/T）、GSTT1缺失基因型（null）和GSTM1缺失基因型（null）个体发生苯中毒的风险最大，可考虑作为苯中毒的重要生物标志物。Objective To explore the relationship between genetic polymorphism of CYP2E1, MPO, NQO1, GSTT1, GSTM1 and susoeptibility to benzene poisoning （BP）. Methods The genotypes of CYP2E1, MPO, NQO1, GSTT1, GSTM1 for 100 potients with benzene poisoning and 90 workers exposed to benzene who were engaged in the same working time and job title as patients with benzene poisoning were detected by PCR-RFLP and multi-PCR. Results There was a 2.82-fold （95 % CI：1.42 - 5.58, P 〈 0.05 ） increased risk of BP in the subjects with NQO1 C609T mutation genotype （T/T） compared with those carrying heterozygeus （C/T） and wild type （C/C）, and there was a 2.94-fold （95 % CI： 1.25 - 6.90, P 〈 0.05） increased risk of BP in the subjects with NQO1 C609T mutation genotype （T/T） compared with those carrying wild type （C/C）. The subjects with GSTT1 null genotype had a 1.91-fold （95% CI：1.05 - 3.45, P 〈 0.05） increased risk of BP compared with those with GSTT1 non-null genotype. Three genes interaction showed that there was a 20.41-fold （95%CI：3.79 - 111.11 ,P 〈 0.01） increased risk of BP in subjects with NQO1 C609T mutation genotype （T/T） and GSTT1 null genotype and GSTM1 null genotype compared with those carrying NQO1 C609T heterozygeus（C/T） and wild type （C/C） and GSTT1 non-null genotype and GSTM1 non-null genotype. Conclusion The interaction of multi-genes may be an important role to BP. The genetic polymorphisms of 3 genes（ NQ01, GSTT1 and GSTM1 ） leaded to declining of ability of detoxifying in benzene metabolism, so the individual with NQO1 C609T mutation genotype（T/T）, GSTT1 null genotype and GSTM1 null genotype is the most susceptive to benzene, h could be suggested as a biomarker to assessment the risk of benzene poisoning for individual.

关 键 词：CYP2E1 MPO NQO1 GSTT1 GSTM1 慢性苯中毒 基因多态 

分 类 号：R994.6[医药卫生—毒理学] Q591[医药卫生—药学]