[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).

CONCLUSION

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.