Genetic polymorphisms involved in toxicant-metabolizing enzymes and the risk of chronic benzene poisoning in Chinese occupationally exposed populations.
Benzene is a recognized haematotoxin and leukaemogen, but its mechanism of action and the role of genetic susceptibility are still unclear. Cytochrome P450 2E1 (CYP2E1) and myeloperoxidase (MPO) are involved in benzene activation; and NAD (P)H:quinine oxidoreductase 1 (NQO1), glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1 (GSTM1) participate in benzene detoxification. The common, well-studied single-nucleotide polymorphisms (SNPs) were analysed in these genes drawn from the toxicant-metabolizing pathways. A total of 100 workers with chronic benzene poisoning (CBP) and 90 controls were enrolled in China. There was a 2.82-fold (95% CI = 1.42-5.58) increased risk of CBP in the subjects with the NQO1 609C > T mutation genotype (T/T) compared with those carrying heterozygous (C/T) and wild-type (C/C). The subjects with the GSTT1 null genotype had a 1.91-fold (95% CI = 1.05-3.45) increased risk of CBP compared with those with GSTT1 non-null genotype. There was no association of CYP2E1 and MPO genotype with CBP. A three genes' interaction showed that there was a 20.41-fold (95% CI = 3.79-111.11) increased risk of CBP in subjects with the NQO1 609C > T T/T genotype and with the GSTT1 null genotype and the GSTM1 null genotype compared with those carrying the NQO1 609C > T C/T and C/C genotype, GSTT1 non-null genotype, and GSTM1 non-null genotype. The study provides evidence of an association of a gene-gene interaction with the risk of CBP.
Chen
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Y
College of Public Health, XinJiang Medical University, Urumqi, China. ychen88@sina.com
Li
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G
Yin
S
S
Xu
J
J
Ji
Z
Z
Xiu
X
X
Liu
L
L
Ma
D
D
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001554:Benzene / Q000378:metabolism* / Q000493:pharmacokinetics / Q000506:poisoning*; D016022:Case-Control Studies; D002681:China; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D016273:Occupational Exposure; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D009195:Peroxidase / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D001554:Benzene; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); D010088:Oxidoreductases; D009195:Peroxidase; C447479:NQO1 protein, human; C413545:glutathione S-transferase T1