Wu Fen, Zhang Zhongbin, Wan Junxiang, Gu Shouyong, Liu Weiwei, Jin Xipeng, Xia Zhaolin
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, China.
Toxicol Appl Pharmacol. 2008 Dec 15;233(3):447-53. doi: 10.1016/j.taap.2008.09.008. Epub 2008 Sep 23.
Oxidative damage to DNA induced by benzene is an important mechanism of its genotoxicity, which leads to chronic benzene poisoning (CBP). Therefore, genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population. We hypothesized that single nucleotide polymorphisms (SNPs) in hMTH1, hOGG1 and hMYH genes are associated with risk of CBP. We genotyped SNPs at codon 83 of hMTH1, codon 326 of hOGG1, and codon 324 of hMYH in 152 CBP patients and 152 healthy workers occupationally exposed to benzene without poisoning manifestations. The genotypes were determined by polymerase chain reaction-restrained fragment length polymorphism (PCR-RFLP) technique. There were 2.51-fold [adjusted odds ratio (OR(adj)), 2.51; 95% CI, 1.14-5.49; P=0.02] and 2.49-fold (OR(adj), 2.49; 95% CI: 1.52-4.07; P<0.01) increased risk of CBP for individuals carrying genotypes of hMTH1 83Val/Met+Met/Met and hOGG1 326Cys/Cys, respectively. Compared with individuals carrying genotypes of hOGG1 326Cys/Cys and hMYH 324His/His at the same time, there was a 0.33-fold (OR(adj), 0.33; 95% CI: 0.15-0.72; P<0.05) decreased risk of CBP for those with genotypes of hOGG1 326Ser/Cys+Ser/Ser and hMYH 324His/Gln+Gln/Gln. In the smoking group, there was a 0.15-fold (OR(adj), 0.15; 95% CI, 0.03-0.68; P=0.01) decreased risk of CBP for subjects carrying genotypes of hMYH 324His/Gln+Gln/Gln compared with those of genotype of hMYH 324His/His. Therefore, our results suggested that polymorphisms at codons 83 of hMTH1 and codon 326 of hOGG1 might contribute to CBP in a Chinese occupational population.
苯诱导的DNA氧化损伤是其遗传毒性的重要机制，可导致慢性苯中毒（CBP）。因此，DNA修复基因的遗传变异可能会影响暴露人群对CBP的易感性。我们假设hMTH1、hOGG1和hMYH基因中的单核苷酸多态性（SNP）与CBP风险相关。我们对152例CBP患者和152名职业性接触苯但无中毒表现的健康工人进行了hMTH1第83密码子、hOGG1第326密码子和hMYH第324密码子的SNP基因分型。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术确定基因型。携带hMTH1 83Val/Met+Met/Met和hOGG1 326Cys/Cys基因型的个体发生CBP的风险分别增加2.51倍[调整优势比（OR(adj)），2.51；95%可信区间（CI），1.14-5.49；P=0.02]和2.49倍（OR(adj)，2.49；95%CI：1.52-4.07；P<0.01）。与同时携带hOGG1 326Cys/Cys和hMYH 324His/His基因型的个体相比，携带hOGG1 326Ser/Cys+Ser/Ser和hMYH 324His/Gln+Gln/Gln基因型的个体发生CBP的风险降低0.33倍（OR(adj)，0.33；95%CI：0.15-0.72；P<0.05）。在吸烟组中，携带hMYH 324His/Gln+Gln/Gln基因型的受试者与携带hMYH 324His/His基因型的受试者相比，发生CBP的风险降低0.15倍（OR(adj)，0.15；95%CI，0.03-0.68；P=0.01）。因此，我们的结果表明，hMTH1第83密码子和hOGG1第326密码子的多态性可能与中国职业人群的CBP有关。
