目的探讨脱嘌呤-脱嘧啶核酸内切酶(APE1)和X线交叉互补基因1(XRCC1)基因多态与氯乙烯致外周血淋巴细胞染色体损伤易感性的关系。方法采用双核淋巴细胞微核的方法评价个体染色体损伤水平,采用引入错配碱基创造酶切位点的限制性片断长度多态(CRS-RFLP)和PCR-RFLP技术对75名氯乙烯接触工人APE1Asp148Glu,XRCC1Arg194Trp、Arg280His及Arg399Gin多态位点进行检测。结果研究对象中APE1 148(Asp/Asp、Asp/Glu、Glu/Glu)三种基因型频率分别为38.7%、44.0%和17.3%;XRCC1 194(Arg/Arg、Arg/Trp、Trp/Trp)三种基因型频率分别为75.5%、21.3%和4.0%;XRCC 1280(Arg/Arg、Arg/Hi、His/His)三种基因型频率分别为69.3%、30.7%和0;XRCC 1399(Arg/Arg、Arg/Gln、Gln/Gln)三种基因型频率分别为49.3%、45.3%和5.3%。多因素poisson回归分析结果表明,女性发生染色体损伤的危险性是男性的1.6倍(95%CI 1.2284~2.0699,P=0.0004),XRCC1 194Arg/Arg基因型个体发生染色体损伤的危险性是Arg/Trp、Trp/Trp基因型个体的0.6898倍,(95%CI 0.4997~0.9333,P=0.0195)。单体型分析结果表明,TGG/CGG和TGG/CAG单体型对组微核率均低于野生纯合子单体型(CGG/CGG)(P〈0.05)。结论女性和XRCC1 194 Arg/Arg基因型个体为氯乙烯致染色体损伤的易感人群。
Objective To explore the relationship between genetic polymorphism of APE1, XRCC 1 and susceptibility of chromosomal damage induced by vinyl chloride monomer(VCM). Methods 75 workers occupationally exposed to VCM were investigated. Chromosome damage in peripheral lymphocyte were measured by cytokinesis-block micronucleus (CBMN) test. Created restriction site -restrained fragment length polymorphism (CRS-RFLP) and PCR-RFLP technique was applied to detect single nucleotide polymorphisms(SNPs) in APE1 gene (c. 148) and XRCC1 gene (c. 194,c .280 and c. 399). Results The frequencies of the Asp and Glu alleles of APEI 148 in our study population were 61% and 39%, respectively. The frequencies of occurrence of the Arg and Trp alleles of XRCC1 194 were 85% and 15%. The frequencies of occurrence of the Arg and His alleles of XRCC1 280 were 85% and 15%, too. Whereas the prevalence of Arg allele was 87.0% and XRCC1 399 allele Gin was 13.0%. The risk of chromosomal damage induced by VCM for individuals carrying XRCC1 c, 194 Arg/Arg genotype was 0. 6898 (95 % C1 0.4997 - 0.9333, P = 0. 0195 ) of those carrying Arg/Trp, Trp/Trp genotypes. The risk of chromosomal damage for female VCM exposure workers was 1. 6000(95 % C1 1.2284 - 2.0699, P = 0.0004)of male workers. The haplotypes TGG/CGG and TGG/CAGCGGG were associated with the decreased frequencies of total micronucleus ( P 〈 0.05 ). Conclusion It was suggested that female workers and subjects carrying XRCC1 194Arg/Arg genotypes could be higher risk of chromosomal damage when they exposed to VCM.