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NQO1、GSTT1和GSTM1基因多态性与慢性苯中毒的遗传易感性 被引量:10

Genetic polymorphisms of NQO1,GSTT1,GSTM1 and susceptibility to chronic benzene poisoning
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摘要 目的探讨NQO1、GSTT1和GSTM1基因多态性与慢性苯中毒遗传易感性之间的关系。方法选择100名慢性苯中毒病例为病例组及90名同期接苯但无苯中毒表现的同工种工人为对照组,应用PCR-RFLP及多重PCR方法判定NQO1、GSTT1和GSTM1基因型。结果携带NQO1C609TT/T基因型(纯合突变型)个体发生苯中毒的危险性是具有C/T基因型(杂合型)和C/C基因型(野生型)个体的2.82倍(95%CI1.42~5.58,P<0.05),是具有C/C基因型(野生型)个体的2.94倍(95%CI1.25~6.90,P<0.05);携带GSTT1缺失(null)基因型个体发生苯中毒的危险性是具GSTT1非缺失(non-null)基因型个体的1.91倍(95%CI1.05~3.45,P<0.05),未发现GSTM1基因型与苯中毒的关系。同时携带NQO1C609TT/T基因型、GSTT1缺失、GSTM1缺失任何两种基因型的个体发生苯中毒的危险性均高于同时携带野生型及非缺失基因型的个体;并且同时携带NQO1C609TT/T基因型、GSTT1缺失与GSTM1缺失个体接苯时发生苯中毒的危险性最高,是NQO1C609TC/T基因型和C/C基因型、GSTT1非缺失型(non-null)与GSTM1非缺失型(non-null)个体的20.41倍(95%CI3.79~111.11,P<0.01)。结论基因之间的交互作用在苯中毒的发生中起重要作用。同时携带NQO1C609TT/T基因型、GSTT1缺失基因型和GSTM1缺失基因型个体发生苯中毒的风险最? Objective To explore the relationship between genetic polymorphism of quinone oxidoreductase 1(NQO1),glutathione S-transferase theta 1(GSTT1),glutathiones S-transferase mu 1(GSTM1) and susceptibility to chronic benzene poisoning(BP). Methods The genotypes of NQO1,GSTT1,GSTM1 for 100 patients with benzene poisoning and 90 workers exposed to benzene who were engaged in the same working time and job title as patients with benzene poisoning were detected by PCR-RFLP and multi-PCR. Results There was a 2.82-fold(95% CI:1.42~5.58,P<0.05) increased risk of BP in the subjects with NQO1 C609T mutation genotype(T/T) compared with those carrying heterozygous(C/T) and wild type(C/C),and there was a 2.94-fold(95% CI:1.25~6.90,P<0.05) increased risk of BP in the subjects with NQO1 C609T T/T genotype compared with those carrying C/C genotype.The subjects with GSTT1 null genotype had a 1.91-fold(95% CI:1.05~3.45,P<~0.05 ) increased risk of BP compared with those with GSTT1 non-null genotype.The interaction of two genes showed that there was a increased risk of BP in subjects with any two genotypes of NQO1 C609T T/T genotype and GSTT1 null genotype and GSTM1 null genotype,compared to the individual with any two genotypes of NQO1 C609T ~C/C genotype and GSTT1 non-null genotype and GSTM1 non-null genotype.The interaction of three genes showed that there was a 20.41-fold(95% CI:3.79~111.11,P<0.01) increased risk of BP in subjects with NQO1 C609T T/T genotype and GSTT1 null genotype and GSTM1 null genotype compared with those carrying NQO1 C609T ~C/T genotype and C/C genotype and GSTT1 non-null genotype and GSTM1 non-null genotype. Conclusions The interaction of multi-genes may be an important role to BP.The genetic polymorphisms of 3 genes(NQO1、GSTT1 and GSTM1) led to declining of detoxifying ability in benzene metabolism,so the individual with NQO1 C609T ~T/T genotype,GSTT1 null genotype and GSTM1 null genotype is most susceptive to benzene.The results were consistent with that of the theoretic presumption.It could be sugg
出处 《中华劳动卫生职业病杂志》 CAS CSCD 北大核心 2005年第1期1-5,共5页 Chinese Journal of Industrial Hygiene and Occupational Diseases
基金 国家自然科学基金资助(No.39870685)
关键词 GSTT1 NQO1 慢性苯中毒 携带 GSTM1基因 个体发生 基因型 C/C 工人 交互作用 Genetic predisposition to disease Poisoning,Benzene
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