ERCC4基因遗传变异对焦炉工外周血淋巴细胞DNA损伤的影响

Influences of excision repair cross complementation group 4 genetic variations on DNA damage in lymphocytes among coke oven workers

目的探讨焦炉作业工人核苷酸切除修复交叉互补组4基因(excision repair cross comple- mentation group 4,ERCC4)多态性和外周血淋巴细胞DNA损伤的关联。方法选择某焦化厂246名焦炉作业工人和127名对照者,运用彗星试验评价外周血淋巴细胞DNA损伤;根据Hapmap数据库筛选ERCC4基因的标签单核苷酸多态性位点(tagged-single nucleotide polymorphisms,TagSNPs),使用Taq- Man-MGB探针荧光标记聚合酶链反应方法对′rs744154、rs3136079及rs31870 3个TagsNPs进行基因分型;运用PHASE2.0.2遗传分析软件计算单体型。结果焦炉工组外周血淋巴细胞的Olive尾矩(Olive TM)高于对照组(对数转换后分别为1.26±1.12及0.52±0.97),差异有统计学意义(P<0.01)。焦炉工中,3个TagsNPs的不同基因型携带者Olive TM值的差异无统计学意义(P>0.05),构建的不同单体型对携带者Olive TM值的差异亦无统计学意义(P>0.05);对照组中rs3136079位点TG杂合子携带者Olive TM值最低(0.26±0.96),明显低于野生型纯合子TT(0.66±0.98)及突变型纯合子GG携带者(0.66±0.51),差异均有统计学意义(P<0.05),构建的CTG/CTG单体型对携带者Olive TM值最高(0.69±1.01),无CTG单体型携带者Olive TM值最低(0.25±0.80),差异无统计学意义(P=0.08)。结论ERCC4基因多态性对焦炉工外周血淋巴细胞DNA损伤程度无影响,但对照组中rs3136079位点TG杂合基因型携带者DNA损伤程度较轻,表明DNA损伤程度受遗传和环境因素交互作用的影响。

Objective To investigate the relationship between excision repair cross complementation group 4 （ERCC4） gene polymorphisms and DNA damage in lymphocytes of coke oven workers and controls. Methods Two hundred and forty-six coke oven workers and one hundred and twenty-seven controls were recruited in the study, and peripheral vein blood was drawn after over night fasting. Comet assay was used to evaluate DNA damage, and TaqMan-MGB probes were used to analyze ERCC4 genetic variations including the three Tagged-single nucleotide polymorphisms （TagSNPs）, referred to rs744154, rs3136079 and rs31870 which were picked out from Hapmap database. Then haplotypes were reconstructed by PHASE2.0.2 software. Results The lymphocytes Olive TM value of coke oven workers was significantly higher than that of controls （1.26± 1.12 vs 0.52± 0.97, P〈0.01）. Among coke oven workers, no significant difference was found between the Olive TM of those with different genotypes or haplotype pairs at ERCC4 gene （P〉0.05）. However, in the control group, the TG genotype carriers had higher Olive TM than the TT and GG genotype carriers （0.26±0.96 vs 0.66±0.98 and 0.66± 0.51, P〈0.05）, and the CTG/CTG haplotype pairs carriers had the highest Olive TM （0.69±1.01）, and no CTG haplotype carriers had the lowest Olive TM （0.25±0.80）, and the difference was borderline （P=0.08）. Conclusion The gene polymorphism at ERCC4 gene has no effects on the DNA damage of lymphocytes in coke oven workers, but the TG genotype carriers has lower DNA damage in the control. DNA damage is influenced by the interaction of genetic and environmental factors.