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目的 探讨毒物代谢酶基因多态性与接触氯乙烯致肝损伤的关系。方法 以肝B 超检查异常或丙氨酸转氨酶 (ALT) >4 0作为肝损伤指标 ,应用聚合酶链反应 (PCR)检测谷胱甘肽转移酶(GSTT1,GSTM1)基因型 ;应用PCR和限制性酶切片段长度多态分析技术 (RFLP)检测细胞色素P4 5 0 2E1酶基因型 (CYP2E1) ,然后对实验结果进行统计分析。结果 尽管GSTT1基因型分布在肝损伤组与对照组比较 ,差异均无显著性 (P >0 .0 5 )。当将低、中接触组合并后 ,阳性型肝损组与对照组比较 ,差异有显著性 (OR为 0 .35 ,95 %CI为 0 .12～ 0 .97,P <0 .0 5 ) ;在高接触损伤组 ,CYP2E1c1c2 /c2c2基因型有更高的频率 ,与对照组比较 ,差异有显著性 (OR为 4 .5 5 ,95 %CI为 1.37～ 15 .0 8,P <0 .0 5 ) ;多元Logistic回归分析显示 ,CYP2E1基因型、氯乙烯接触与CYP2E1基因型 ,CYP2E1与GSTT1基因型 ,GSTT1与GSTM 1基因型间的联合作用与肝脏损伤有关联 ,经 χ2 检验 ,P <0 .0 5。结论 高剂量接触氯乙烯时 ,CYP2E1c1c2 /c2c2基因型在氯乙烯致肝损伤方面可能是主要易感性原因之一 ,而GSTT1在氯乙烯代谢中可起到解毒作用 ,尤其在低剂量接触时有保护作用。本研究结果初步表明 ,毒物代谢酶基因间联合作用与累积接触剂量 ,最终决定毒物是否产生危害?
Objective To investigate the relationship between polymorphisms of the toxicant metabolic enzyme gene and liver injury induced by exposure to vinyl chloride. Methods Hepatitis B injury was detected by abnormal liver B-ultrasound or alanine aminotransferase (ALT) >40. Polymerase chain reaction (PCR) was used to detect GSTT1, GSTM1 genotypes; PCR and restriction were used. Fragment length polymorphism analysis (RFLP) was used to detect cytochrome P4520E1 genotype (CYP2E1), and then the experimental results were analyzed statistically. Results Although the GSTT1 genotype distribution in the liver injury group compared with the control group, there was no significant difference (P > 0.05). When the combination of low and middle exposures was combined, there was a significant difference between the positive liver damage group and the control group (OR was 0.35, 95% CI was 0.12 to 0.97, P<0.05). In the high-contact injury group, there was a higher frequency of CYP2E1c1c2/c2c2 genotype compared with the control group, with a significant difference (OR, 4.55, 95% CI, 1.37 to 15.08, P<0. Multivariate logistic regression analysis showed that the combined effects of CYP2E1 genotype, vinyl chloride exposure and CYP2E1 genotype, CYP2E1 and GSTT1 genotypes, and GSTT1 and GSTM1 genotypes were associated with liver injury. The χ2 test showed that P < 0 .0 5. Conclusion When high doses of vinyl chloride are exposed, the CYP2E1c1c2/c2c2 genotype may be one of the main susceptibility factors in the liver injury induced by vinyl chloride, while GSTT1 may play a detoxifying role in the metabolism of vinyl chloride, especially when it is exposed at low doses. effect. The results of this study have initially shown that the combined effects of toxic metabolic enzymes and cumulative exposure doses ultimately determine whether the toxicants are harmful.