目的探讨氯乙烯(VCM)致DNA损伤与DNA修复基因和代谢酶基因多态性的关系。方法彗星试验检测DNA损伤,并按DNA损伤情况将接触VCM的研究对象分为DNA损伤组(75人),采用病例对照设计方法选择对照组(75人),用聚合酶链反应一限制性酶切片段多态性技术(PCR.RFLP)和PCR测XRCCl(Arg94Trp,Arg280His和Arg399Gln)、XPD(Ile199Met,Asp312Asn和Lys751Gin)和代谢酶(CYP2E1、GSTTI和GSTMI)基因多态性。结果单因素分析结果表明,CYP2E1clc2、c2c2和XPD751Lys/Gln、Gln/Gln基因型携带者DNA损伤风险明显增高,而XRCCI399Arg/Gln、Gln/Gln基因型携带者DNA损伤风险明显降低,差异均有统计学意义(P〈0.05,P〈0.01)。logistic回归分析发现,XRCCI194、XRCCI399、XPD751和CYP2E1多态与DNA损伤有关。累积接触剂量分析表明,具XRCCI399Arg/Gln、Gln/Gln基因型个体即使在累积接触剂量高的情况下DNA损伤发生率仍明显降低(OR:0.35,95%CI:0.12~1.01);具CYP2E1cl/c2、c2/c2基因型个体,无论累积接触剂量高低,其DNA损伤发生率均明显高于对照(OR:2.57,95%CI:1.01—6.59和OR:2.57,95%Ch0.99—6.87)。结论VCM累积接触剂量和CYP2E1、XRCCI194、XRCCI399及XPD751基因型与VCM诱导的DNA损伤有关。
Objective To explore the association between DNA damage induced by vinyl chloride monomer (VCM) and polymorphisms of DNA repair genes and xenobiotic metabolism genes of VCM. Methods Comet assay was employed to detect DNA damage. Based on the status of DNA damage, the VCM exposure workers were divided into two groups: DNA damage group (75) and control group (75). Case-control design was used to investigate the association between the genetic polymorphisms and DNA damage induced by VCM. Genotypes ofXRCCl(Argl94Trp, Arg280His and Arg399Gln), XPD (Ile199Met, Asp312Asn and Lys751Gln) and CYP2E1 were identified by the PCR-RFLP. PCR assay was used to detect positive and null genotype of GSIT1 and GSTM 1. Results Univariate analysis showed that the CYP2E1 c 1 c2/c2c2 and XPD751 Lys/Gln and Gin/Gin genotypes were significantly associated with the increased levels of DNA damage, XRCCI 339 Arg/Gln and Gin/Gin genotypes were significantly associated with the decreased levels of DNA damage(P〈0.01, P〈0.05, respectively). Logistic regression analysis showed that there was significant association between the genotypes of XRCCI 194,XRCC1 399, XPD 751, CYP2E1 and DNA damages. A prominent risk decreasing of DNA damage was observed for those individuals possessing XRCC1 399Arg/Gln +Gln/Gln genotypes (OR: 0.35,95% CI:0.12 -1.01, respectively); The results also showed that there were significant associations be- tween CYP2E1 clc2/c2c2 and DNA damage both in high and low VCM-exposed groups (OR :2.57, 95% CI: 1.01-6.59 and 0R:2.57,95% CI: 0.99~6.87 ). Conclusion Cumulative exposure dose and genotypes of XR- CC1 194, XRCC1 399, XPD 751 and CYP2E1 may modulate the DNA damage induced by VCM exposure.