[Relationship between genetic polymorphisms of phase I and phase II metabolizing enzymes and DNA damage of workers exposed to vinyl chloride monomer].
OBJECTIVE
To investigate the association between genetic polymorphisms in phase I and phase II metabolism genes and DNA damage in peripheral blood lymphocytes of workers exposed to vinyl chloride monomer (VCM).


METHODS
87 workers occupationally exposed to VCM were investigated. DNA damage in peripheral blood lymphocytes was measured by Comet Assay; the workers were divided into case, control groups based on the comet frequency. Genotypes of CYP2E1 (rs3813867) were identified by the PCR-RFLP, null genotypes of GSTT1 and GSTM1 were detected by PCR. The genotype of GSTP1 (rs947894), CYP1A1 (rs1048943, rs4646903) and UGT1A6 (rs6759892, rs1105879, rs4124874, rs3755319, rs887829, rs4148323) were tested by the TaqMan PCR method.


RESULTS
The distribution of the c1c1 and c1c2 + c2c2 genotype of CYP2E1 (rs3813867), AA and AG + GG genotype of GSTP1 (rs947894), AA and AC + CC genotype of UGT1A6 (rs1105879) were significantly different in DNA damage group and control group by chi2 test (P = 0.029, P = 0.004 and P = 0.002, respectively). Multiple logistic regression analysis showed that the individuals carrying GSTP1 (rs947894) AG + GG genotypes had 13.393-fold (95% CI: 2.410-74.431, P < 0.01) increased risk of DNA damage in comparison with those with GSTP1 AA genotypes, and individuals carrying UGT1A6 (rs1105879) AC + CC genotypes had 0.064-fold (95% CI: 0.006-0.637, P < 0.05) decreased risk of DNA damage in comparison with those with UGT1A6 (rs1105879) AA genotypes. Haplotypes analysis of polymorphisms in UGT1A6 showed that the frequencies of TCCTAG haplotype in the controls were significant higher than those in the cases (P < 0.05).


CONCLUSIONS
The subjects carrying GSTP1rs947894 AG/GG genotypes and UGT1A6 rsl105879 AA genotypes could be more susceptible to VCM-induced DNA damage. UGT1A6 TCCTAG haplotype may be a protective genetic factor for DNA damage in VCM-exposed workers.
Ji
Fang
F
Department of Occupational Health, School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai 200032, China. jifang_1212@163.com
Zhu
Shoumin
S
Sun
Pin
P
Wang
Wei
W
D000328:Adult; D002617:Chemical Industry; D020552:Comet Assay; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D014752:Vinyl Chloride / Q000009:adverse effects*; D055815:Young Adult
D019392:Cytochrome P-450 CYP2E1; D014453:Glucuronosyltransferase; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D014752:Vinyl Chloride; C110655:UDP-glucuronosyltransferase, UGT1A6; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human