Genetic polymorphisms of NQO1, GSTT1, GSTM1 and susceptibility to chronic benzene poisoning

Abstract

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). 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. There was a 2.82-fold (95% CI: 1.42 approximately 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 approximately 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 approximately 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 approximately 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. 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 suggested as a biomarker to assess the risk of benzene poisoning for individuals.