XRCC1基因单核苷酸多态性与铅毒性遗传易感性的关系

目的研究DNA修复基因XRCC1单核苷酸多态性与铅毒性易感性的关系。方法采集326名某蓄电池企业铅作业工人外周静脉血样品,检测血铅和血锌原卟啉(ZPP),采用聚合酶链式反应-限制性片段长度多态(PCR-RFLP)检测XRCC1基因型,分析不同基因型铅作业工人与铅毒性易感性的关系。结果 326名铅作业工人XRCC1基因分布呈现多态现象,各基因型的分布频率符合遗传学的Hardy-Weinberg平衡(P>0.05);不同基因型组(XRCC1-194CC/CT+TT、XRCC1-280 GG/GA+AA、XRCC1-399GG/GA+AA)工人ZPP差异无统计学意义(P>0.05);XRCC1-194CT+TT基因型组工人平均血铅值高于XRCC1-241CC基因型组(P<0.05),而XRCC1-280GG/GA+AA、XRCC1-399GG/GA+AA基因型组工人平均血铅值差异无统计学意义(P>0.05);以血铅水平1.90μmol/L为界,经χ2检验、logistic回归分析显示,高铅组XRCC1-194CT+TT基因型的比例大于低铅组(P<0.05),XRCC1-194CT+TT基因型组工人较XRCC1-194CC基因型组工人高血铅发生率的风险明显增高(OR=2.78,95%CI=1.49～5.28)。结论XRCC1 Arg194Trp基因单核苷酸多态性与血铅升高有一定关联性,C→T多态性提高了接铅工人对铅毒性易感的风险性,XRCC1-194CT/TT基因型可能是铅毒性易感基因型;XRCC1 Arg280His和XRCC1 Arg399Gln多态性可能与铅毒性易感性无关。

Relationship between genetic susceptibility to lead toxicity and single nucleotide polymorphisms in XRCC1 gene

Objective To explore the relationship between gene polymorphisms of XRCC1 and susceptibility to lead toxicity.Methods 326 blood samples of lead-exposed workers from a storage battery factory in Fuzhou were taken,lead and ZPP levels in blood were analyzed.An assay based on the polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique of restriction enzyrne was used to determine the genotype of the XRCC1 gene,then the relationship between XRCC1 polymorphisms and the susceptibility to lead toxicity was studied by genotypes.Results The distribution frequencies of alleles and genotypes of XRCC1 in 326 lead-exposed workers accorded with Hardy-Weinberg equilibrium(P>0.05),the differences of blood ZPP levels among different genetypes(XRCC1-194CC/CT+TT,XRCC1-280GG/GA+AA,XRCC1-399GG/GA+AA)showed no significant significance(P>0.05),the blood lead level of XRCC1-194CT+TT genotype was higher than that of XRCC1-194CC genotype(P<0.05),however,the differences of blood lead levels between the genetypes XRCC1-280GG/GA+AA and XRCC1-399GG/GA+AA was no statistical significance(P>0.05),while in high blood lead group(>1.90 μmol/L)the proportion of XRCC1-194CT+TT genotype was higher than that of XRCC1-194CC(P<0.05),and the workers with XRCC1-194CT+TT genotype had an increased risk of high blood lead(OR=2.78,95%CI=1.49～5.28).Conclusion The results showed that there is some correlation between XRCC1Arg194Trp polymorphisms and blood lead level,and the polymorphism of C changes to T increase the risk of susceptivity to lead toxicity,and the XRCC1-194CT/TT genotype may be the susceptible genotype to lead toxicity,while the XRCC1Arg280His and XRCC1Arg399Gln polymorphisms is probably not the susceptible factor to lead toxicity.