NER通路基因多态与氯乙烯所致微核率改变关系的研究  

Association between Polymorphisms in NER Pathway Genes and Vinyl Chloride-Induced Chromosomal Damage

作　　者：徐晓文[1] 王金玮[1] 王琪[1] 张放[2] 孙原[1] 冯楠楠[1] 周莉芳[1] 邵华[2] 夏昭林[1] 

机构地区：[1]复旦大学公共卫生学院劳动卫生与毒理学教研室、公共卫生安全教育部重点实验室,上海200032 [2]山东省职业卫生与职业病防治研究院职业卫生检测评价中心,山东250062

出　　处：《环境与职业医学》2013年第10期733-740,共8页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金项目(编号:NSFC30671740)

摘　　要：[目的]探讨核苷酸切除修复(NER)通路修复基因多态与氯乙烯(vinyl chloride,VC)所致外周血淋巴细胞染色体损伤的关系。[方法]采用胞质分裂阻滞微核试验评价317名氯乙烯作业工人(接触组)和166名对照组工人的染色体损伤水平,利用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)检测NER通路中5个关键基因的7个常见位点的多态,分析各基因多态与氯乙烯接触工人染色体损伤的关系,以及氯乙烯暴露剂量和各基因多态之间的交互作用。[结果]接触组的微核率为(3.47±2.65)‰,高于对照组(2.51±1.96)‰(P<0.05)。接触组XPA Ala23Gly,XPC Ala499Val,XPC Lys939Gln,XPF 5′-UTR T2063A四个单核苷酸位点多态均与遗传易感性有关(FR及其95%CI分别为1.20、1.05～1.39,1.17、1.04～1.32,1.23、1.09～1.38,0.75、0.64～0.91,均P<0.01),且与累积接触剂量之间存在交互作用。此外,XPC(PAT)(-499)(-939)单体型分析显示,PAT-CG/PAT-TG,PAT+TG/PAT+TG,PAT+CA/PAT+CA以及PAT+TG/PAT+TA微核率显著高于PAT-CA/PAT-CA(FR及其95%CI分别为2.45、2.01～3.75,1.08、1.02～1.32,1.35、1.13～1.57,1.57、1.02～1.96,P<0.01或P<0.05);而PAT-CA/PAT+CA的微核率显著低于PAT-CA/PAT-CA(FR为0.25,95%CI为0.12～0.57,P<0.01)。[结论]在工作场所空气VC浓度低于我国现行职业限值的情况下,VC仍可致作业工人染色体损伤;NER通路某些损伤修复基因多态可能与VC致染色体损伤有关。[ Objective ] To explore the association between polymorphisms in nucleotide excision repair （NER） pathway genes and vinyl chloride （VC）-induced chromosomal damage in peripheral blood lymphocytes. [ Methods ] Cytokinesis-block micronucleus （CBMN） assay was used to detect chromosomal damage in peripheral lymphocytes of 317 VC-exposed workers and 166 controls. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was used to detect 7 single nucleotide polymorphisms （SNPs） of 5 critical genes in NER pathways. The associations of these polymorphisms with chromosomal damage as well as the gene-exposure interaction were then analyzed. [ Results ] The mean micronucleus frequency in the exposure group was （3.47 ± 2.65）‰, which was higher than that of the control workers [ （2.51 ± 1.96）‰] （P 〈 0.01）. The SNPs ofXPA Ala23Gly, XPC A la499 Val, XPC Lys939Gln, and XPF 5＇UTR T2063A were associated with the micronueleus （MN） frequency as an indicator of susceptibility （FR and 95%CI： 1.20, 1.05-1.39; 1.17, 1.04-1.32; 1.23, 1.09-1.38; 0.75, 0.64-0.91, all P〈0.01, respectively）, and interacted with VC cumulated exposure doses. Moreover, the results of haplotype analysis showed higher MN frequencies in the workers carrying the PAT-CG/PAT- TG, PAT＋ TG/PAT＋ TG, PAT＋CA/PAT＋CA or PAT＋ TG/PAT＋ TA diplotype than the workers carrying the wild-type PAT-CA/PAT-CA （FR and 95%CI： 2.45, 2.01-3.75; 1.08, 1.02-1.32; 1.35, 1.13-1.57; 1.57, 1.02-1.96, P〈0.01 or P〈0.05, respectively）; while the workers with PAT-CA/PAT＋CA had lowered risks of the studied damage （FR=0.25, 95%CI： 0.12-0.57, P〈0.01）. [ Conclusion ] VC can induce chromosomal damage even when the exposure level is lower than the national occupational health standard of China. The polymorphism of DNA repair genes in NER pathway may be associated withchromosomal damage induced by VC.

关 键 词：氯乙烯 染色体损伤 胞质分裂阻滞微核试验 DNA损伤修复基因 遗传易感性 

分 类 号：TQ325.3[化学工程—合成树脂塑料工业] R114[医药卫生—卫生毒理学]