XRCC1和APE1基因多态性对氯乙烯致染色体损伤的影响

Effects of polymorphisms in XRCC1 and APE1 on vinyl chloride-induced chromosome damage

目的 探讨XRCC1和APE1基因多态性在氯乙烯（vinyl chloride,VC）所致外周血淋巴细胞染色体损伤中的作用.方法 以山东省某工厂317名VC作业工人为研究对象,以外周血淋巴细胞微核率作为染色体损伤的效应指标,应用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RFLP）和创造酶切位点的限制性片断长度多态性（CRS-RFLP）法对VC接触工人的XRCC1和APE1基因的多态位点进行检测,分析各基因多态位点及XRCC1单倍型与染色体损伤之间的关系.结果 与野生纯合型比较,XRCC1 （-77C/T,Arg 194Trp,Arg280His,Arg399Gln）突变型携带者微核率明显升高,FR值及其可信区间分别为（FR=1.21,95％CI：1.05～1.39,P＜0.05;FR=1.14,95％CI：1.00～1.38,P＜0.05;FR=1.26,95％CI：1.11～1.44,P＜0.05; FR=1.23,95％CI：1.08～1.46; P＜0.05）.APE1 Asp148Glu基因多态与微核率无明显相关性.XRCC1单倍型分析结果显示,CTAA/CTAA和CCAA/CTAA双体型的个体微核率较TCGG/TCGG野生双体型明显升高,FR值及其可信区间分别为（FR=1.19,95％CI：1.02～1.32,P＜0.05和FR=1.41,95％CI：1.02～1.87,P＜0.05）.校正年龄、性别、吸烟、饮酒后,XRCC1（-77C/T、Arg 194Trp、Arg280His、Arg399Gln）基因多态与VC累积接触剂量之间存在交互作用.结论 在我国现行职业卫生标准下（PC-TWA：10mg/m3）,VC仍可对遗传物质造成损伤;XRCC1和APE1基因多态与VC致染色体损伤有关.

Objective To evaluate the effects of polymorphisms in XRCC1 and APE1 genes on vinyl chloride （VC）-induced chromosomal damage in peripheral lymphocytes.Methods In this study,317 workers occupationally exposed to VC were recruited from a factory in Shandong Province,China.The micronucleus （MN） frequency in peripheral lymphocytes was used as an indicator of chromosomal damage.Polymerase chain reaction-restriction fragment length polymorphism and created restriction site combined with restriction fragment length polymorphism were used to determine the five single nucleotide polymorphisms in XRCC1 and APE1 genes in the base excision repair pathway.The association of chromosomal damage with these polymorphisms and the haplotype of XRCC 1 was analyzed using Poisson regression and PHASE 2.0.2.Results It was found that among the VC-exposed workers,individuals with XRCC 1 polymorphisms （-77C/T,Arg 194Trp,Arg280His,and Arg399Gln） had a significantly higher MN frequency than those with homozygous wild-type genotypes,with frequency ratios （FR） as follows,respectively：FR=1.21,95％CI：1.05～1.39 （P＜0.05）; FR=1.14,95％CI：1.00～1.38 （P＜0.05）; FR=1.26,95％CI：1.11～1.44 （P＜0.05）; FR=1.23,95％CI：1.08～1.46 （P＜0.05）.APE1 Asp148Glu was found of no significant relationship with MN frequency.Haplotype analysis of XRCC1 demonstrated that the MN frequencies in subjects with CTAA/CTAA and CCAA/CTAA were significantly higher than that in those with TCGG/TCGG （FR=1.19,95％CI：1.02～1.32,P＜0.05; FR=1.41,95％CI：1.02～1.87,P＜0.05）.Furthermore,association was found between accumulated exposure to VC and XRCC1 polymorphisms （-77C/T,Arg194Trp,Arg280His,and Arg399Gln） after adjustment for age,sex,drinking,and smoking.Conclusion VC can induce chromosomal damage even when the exposure level is lower than the national occupational health standard of China （PC-TWA：10 mg/m3）; the polymorphisms in XRCC1 and APE1 are associated with chromosomal damage induced by VC.