GSTM1和CYP2E1基因多态对慢性苯中毒易感性的影响

Effect of GSTM1 and CYP2E1 Genetic Polymorphisms on Susceptibility to Chronic Benzene Poisoning

[目的 ]苯对造血功能的损害主要是由其中间代谢产物酚类和醌类化合物产生的 ,CYP2E1和GSTM1是分别在苯代谢活化和解毒过程中发挥重要作用的代谢酶。本研究旨在探讨CYP2E1和GSTM1基因多态性和慢性苯中毒易感性的关系。 [方法 ]以某钢铁公司 6 5名慢性苯中毒的工人作为病例组 ,以 6 3名没有发生中毒的苯作业工人作对照组进行病例对照研究。采用PCR和RFLP的方法检测GSTM1和CYP2E1的基因多态性。 [结果 ]病例组中GSTM1缺失型的比例高于对照组 ( 4 6 5 5 %和 2 4 5 6 % ,P <0 0 5 )。而在低累积接触评分组 ,GSTM1缺失型的个体发生慢性苯中毒的风险性是阳性型的 3 99倍 (P <0 0 1)。将CYP2E1和GSTM1进行联合作用分析 ,结果提示在CYP2E1基因 96bp插入阳性型的个体中 ,同时携带GSTM1缺失型的个体更易发生慢性苯中毒 (OR =3 75 ,95 %CI :0 86～ 17 2 7,P <0 0 5 )

Benzene hematotoxicity is mainly caused by its intermediates such as phenol and quinones. Cytochrome P450 2E1(CYP2E1) and glutathione s transferase M1(GSTM1) are important metabolizing enzymes involved in benzene activation and detoxification. A case control study was conducted to explore the association between genetic polymorphisms of CYP2E1,GSTM1 and susceptibility to chronic benzene poisoning. The cases were 65 patients with chronic benzene poisoning,they were workers in a Steel & Iron Group,and the controls were 63 benzene exposed workers in the same exposure environment. PCR and/or RFLP (restriction fragment length polymorphism) were used to detect the GSTM1 and CYP2E1 genetic polymorphisms. The results showed the proportion of GSTM1 null genotype in cases is higher than that of controls (46 55% vs 24 56%, P <0 05). Moreover,in group of low cumulative exposure score the individuals with GSTM1 null genotype had a 3 99 fold increased risk of chronic benzene poisoning compared with the individuals with GSTM1 non null genotype ( P <0 01). The interaction of genetic polymorphisms of CYP2E1 and GSTM1 on susceptibility to chronic benzene poisoning was analyzed and our finding suggested that the individuals carrying both one or two copies of CYP2E1 96bp insertion and GSTM1 null genotype could be more susceptible to benzene toxicity( OR=3 75,95%CT:0 86～17 27,P <0 05).