Genetic polymorphisms in hMTH1, hOGG1 and hMYH and risk of chronic benzene poisoning in a Chinese occupational population.

Abstract:

: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.

journal_name

Toxicol Appl Pharmacol

authors

Wu F,Zhang Z,Wan J,Gu S,Liu W,Jin X,Xia Z

doi

10.1016/j.taap.2008.09.008

subject

Has Abstract

pub_date

2008-12-15 00:00:00

pages

447-53

issue

3

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(08)00393-1

journal_volume

233

pub_type

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