CYP2E1和MPO基因单核苷酸多态性对慢性苯中毒危险性的影响  

Effect of SNPs of CYP2E1 and MPO Genes on Risks of Chronic Benzene Poisoning

作　　者：万俊香[1] 施锦绣[2] 高晓玲[3] 管继如[4] 刘薇薇[5] 曹多志 金锡鹏[1] 胡赓熙[2] 夏昭林[1] 

机构地区：[1]复旦大学公共卫生学院,上海200032 [2]中国科学院细胞所,上海200031 [3]上海市第一人民医院 [4]杭州市疾病控制中心 [5]广州市职业病防治院 [6]马鞍山钢铁公司医院劳研所

出　　处：《环境与职业医学》2002年第1期20-23,共4页Journal of Environmental and Occupational Medicine

基　　金：卫生部青年科研基金 (96Q0 30 ) ;教育部回国人员资助项目(1 999)

摘　　要：[目的 ]本文旨在探讨CYP2E1(cytochromeP45 0 2E1)和MPO(myeloperoxidase)基因单核苷酸多态性与苯中毒易感性的关系。 [方法 ]以 15 6名慢性苯中毒工人作为病例组 ,以 15 2名接触苯而未中毒的工人作为对照组。用PCR、测序和DHPLC等分子生物学技术检测CYP2E1和MPO基因上的SNP ,比较病例组、对照组间的差别。 [结果 ]在男性苯中毒者中 ,MPO基因的c . 463G/A基因型的比例为 2 2 95 % ,高于对照组的 7 14 % (OR =3 87,95 %CI :1 0 8～ 15 0 9,P <0 0 5 )。在经常吸烟的研究对象中 ,携带CYP2E1基因c . 12 93G/C或C/C基因型的个体发生苯中毒的危险性是G/G基因型的 3 3 0倍 (95 %CI :0 88～ 12 71,P <0 0 5 )。 [结论 ]具有CYP2E1基因c . 12 93C/C或C/G基因型而又经常吸烟的个体可能对苯中毒性较易感。男性苯中毒者MPO基因c . 463G/A基因型高频率与理论推断不符 ,提示苯中毒的发生可能是多基因、多因素 (如生活方式等 )Cytochrome P450 2E1( CYP2E1 ) and myeloperoxidase( MPO ) are two important metabolizing enzymes involved in benzene activation. Some studies showed that genotypes of CYP2E1 and MPO were polymorphically distributed among populations. The purpose of this study was to explore the association between single nucleotide polymorphisms (SNPs) of CYP2E1,MPO and risks of chronic benzene poisoning (BP). A case control study was conducted,156 BP workers as a case group and 152 similarly benzene exposed workers who never suffer from BP as a control group. PCR,DNA sequencing and DHPLC (denaturing high performance liquid chromatography) were used to detect the SNPs of promoter and complete coding region of CYP2E1 and MPO genes. The proportion of male subjects with MPO c. 463 G/A genotype was higher than that of male subjects with MPO c. 463 G/G genotype (22 95% vs 7 14%, P <0 05) with OR of 3 87(95% CI :1 08～15 09, P <0 05). Of the subjects exposed to benzene who frequently smoke,a 3 30 fold increased risk of BP was observed among the individuals with CYP2E1 c. 1293 G/C or C/C genotypes compared with the individuals with the CYP2E1 c. 1293 G/G genotype (95% CI :0 88～12 71, P <0 05). [Conclusion] The result suggested the subjects who carry CYP2E1 c. 1293 G/C or C/C genotype and together with the habit of smoking could be more susceptible to benzene toxicity. The inconsistence of male BP subjects with high frequency of MPO c. 463 G/A genotype may be due to the interaction of the mutated gene and other genes as well as environmental factors,such as exposure and lifestyle etc.

关 键 词：慢性苯中毒 CYP2E1 MPO 基因多态性 生活方式 

分 类 号：R135.12[医药卫生—劳动卫生]