核苷酸切除修复基因ERCC1、XPD和XPC多态性与燃煤污染型地方性砷中毒的关系研究

目的 探讨核苷酸切除修复基因ERCCI、XPD、XPC不同基因型与燃煤污染型砷中毒发病风险的关系.方法 以贵州省兴仁县交乐村燃煤污染型砷中毒病区229例砷中毒患者作为病例组,以有相似生活习惯、无燃用高砷煤史的非砷暴露村大果朵村198名居民作为对照组,每人抽取外周静脉血约2 ml提取DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术进行ERCC1 C8092A 、XPD Lys751 Gln、XPD Asp312Asn、XPD Arg156Arg、XPC P(AT+/-)多态位点检测.结果 病例组ERCC1 C8092A位点CA/AA基因型分布频率[ CA:29.78％ (67/225)、AA:10.67％ (24/225)]显著高于对照组[CA:23.08％( 45/195)、AA:5.13％ (10/195),x2=8.116,P＜0.05]；其余各基因多态位点的基因型分布频率差异无统计学意义(x2值分别为5.649、4.394、0.865、1.490,P均＞0.05).携带ERCCI 8092CA+ AA、XPD Lys751Gln+ Gln751Gln 、XPD Asp312Asn+ Asn312Asn基因型个体分别较携带ERCC1 8092CC、XPD Lys751Lys、XPD Asp312Asp基因型个体发生砷中毒的风险升高1.780、1.681、1.790倍(95％CI分别为1.174～2.698、1.081～2.615和1.014～3.158,P均＜0.05)；单一的XPD 基因Arg156Arg位点、XPC基因P(AT+/-)位点对砷中毒的发病风险没有影响(P均＞0.05).结论 核苷酸切除修复基因ERCC1 C8092A、XPD Lys751 Gln和Asp312Asn位点的多态性与燃煤污染型砷中毒的发病风险有关.

Relationship between the genetic polymorphisms in nucleotide excision repair genes of ERCC1, XPD, XPC and the arsenism caused by coal-burning

Objective To investigate the relationship between genetic polymorphisms in excision repair cross-complementing 1 (ERCC 1 ),xeroderma pigmentosum group D (XPD),xeroderma pigmentosum group C (XPC) and the risk of arsenism caused by coal-burning.Methods Two hundred and twenty-nine patients with arsenism in the endemic area of Jiaole village Xingren county Guizhou province were selected into experimental group.One hundred and ninety-eight inhabitants who had similar living habits but did no burning coal with high arsenic in Dagnoduo village were selected into control group.Two milliliters vein blood samples were taken and analyzed with polymerase chain reaction-restriction frgment length polymorphism technique (PCR-RFLP) to measure the gene polymorphisms of ERCC1 C8092A,XPD Lys751Gln,XPD Asp312Asn,XPD Arg156Arg,and XPC P(AT +/-).Relationship between genotype and the risk of arsenism was also analyzed.Results The frequency of ERCC1 8092CA/AA geno-type in case group [ CA:29.78％ (67/225),AA:10.67％ (24/225) ] was significantly higher than that of control group[CA:23.08％(45/195),AA:5.13％(10/195),x2 =8.116,P ＜ 0.05].The frequency difference of other gene polymorphisms between case and control group was not statistically significant,respectively (x2 =5.649,4.394,0.865,1.490,all P ＞ 0.05).There were 1.780(95％CI:1.174 - 2.698),1.681(95％CI:1.081 - 2.615),and 1.790(95％CI:1.014 - 3.158)-fold increase in risk of arsenism for individuals carrying ERCC1 8092CA + AA,XPD Lys751Gln + Gln751Gln,and XPD Asp312Asn + Asn312Asn genotypes compared respectively with individuals canying ERCC1 8092CC,XPD Lys751Lys,and XPD Asp312Asp(all P ＜ 0.05).The sufferers only with XPD Arg156Arg or XPC P(AT +/-) didn't have higher risk of arsenism(all P ＞ 0.05).Conclusion The results of this study suggest that the gene polymorphisms of ERCC1 C8092A,XPD Lys751Gln,and Asp312Asn are related to the arsenism caused by coal-burning.