19q13相邻基因多态性与慢性苯中毒发病风险关联的病例对照研究

Control study on the association of polymorphisms in 19q13 and the risk of chronic benzene poisoning

目的探讨共同位于19q13基因ERCC1,ERCC2,XRCC1,PPP1R13L,CD3EAP的单核苷酸多态性(SNP)与慢性苯中毒(CBP)发病风险的关联,找寻慢性苯中毒易感人群的生物标志,并为CBP的早期防治提供科学理论依据。方法 CBP确诊患者100例,按照1∶2匹配同样接触苯的健康对照200例,采集血样2 ml,提取DNA,采用SNa Pshot检测XRCC1 rs25489,PPP1R13L rs1005165及rs1970764;Taq Man Real time PCR探针法检测ERCC1rs11615,ERCC2 rs13181、rs1799793、rs238406,XRCC1 rs25487、rs1799782及CD3EAP rs967591多态基因型。结果ERCC1 rs11615,XRCC1 rs1799782,XRCC1 rs25487多态性与慢性苯中毒发病风险相关,ERCC1 rs11615 TT和XRCC1rs25487 TT基因型均可使CBP发生风险增高(ORa=3.236,95%CI 1.353~7.740,χ~2=6.875,P=0.009;ORa=2.093,95%CI 0.966~4.533,χ~2=5.642,P=0.018),XRCC1 rs1799782 AA和AG基因型均可使CBP发生风险降低(ORa=0.074,95%CI 0.034~0.160,χ~2=45.128,P=0.000;ORa=0.357,95%CI 0.195~0.653,χ~2=12.168,P=0.000)。尚未发现其他基因多态与CBP发病风险的关联。结论在相同苯作业环境下,携带ERCC1 rs11615 TT、XRCC1 rs25487 TT基因型的个体发生慢性苯中毒的风险增高,上述基因多态可能成为预测慢性苯中毒的生物学标志。

Objective To investigate the association between the single nucleotide polymorphisms（ SNPs） in 19q13 and the susceptible biomarkers of chronic benzene poisoning（ CBP） in an occupational exposed population. Methods 1 ∶ 2 casecontrol study including 100 CBP patients and 200 healthy workers were matched by gender,age and exposure period to benzene. The demographic characteristics and lifestyle（ smoking,drinking） were investigated. After informed consent 2 ml blood samples were collected. After DNA extraction the genotypes of ERCC1,ERCC2,XRCC1,PPP1R13 L,CD3EAP SNP were detected by SNa Pshot technique and Taq Man real time PCR probe method. Results The results showed that there was a close correlation between ERCC1 rs11615,XRCC1 rs1799782,rs25487 and the risk of CBP. ERCC1 rs11615 TT can increase the risk of CBP（ ORa = 3. 236,95% CI 1. 353～7. 740,χ^2= 6. 875,P = 0. 009）,XRCC1 rs25487 TT genotype can increase the risk of CBP（ ORa = 2. 093,95%CI 0. 966～ 4. 533,χ^2= 5. 642,P = 0. 018）. XRCC1 rs1799782 AA and AG genotype can decrease the risk of CBP,AA（ ORa = 0. 074,95%CI 0. 034 ～ 0. 160,χ^2= 45. 128,P = 0. 000）,AG（ ORa = 0. 357,95% CI 0. 195 ～0. 653,χ^2= 12. 168, P = 0. 000）, but there seems no significance between polymorphism of ERCC1 rs3212986, ERCC2rs13181,rs1799793,rs238406, XRCC1 rs25489, PPP1R13 L rs1970764, rs1005165, CD3 EAP rs967591 and the risk of CBP. Conclusion Under the same benzene exposure period,people carrying ERCC1 rs11615 TT genotype,XRCC1 rs25487 TT genotypes were found an increased risk of chronic benzene poisoning. These two polymorphisms may be used as valid biomarkers to predict the risk of CBP. XRCC1 rs1799782 AA and AG can decrease the risk of CBP,which may contribute to the prevention of chronic benzene poisoning.