[Association between methylenetetrahydrofolate reductase gene haplotypes and the susceptibility of chromosomal damage in coke-oven workers].
OBJECTIVE
To investigate the association between MTHFR gene variances and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers exposed to polycyclic aromatic hydrocarbons (PAHs).


METHODS
One-hundred and forty coke-oven workers who exposed to a high level of PAHs and sixty-six non-exposed controls were selected as the study subjects. Chromosomal damage in peripheral lymphocyte was measured by the cytokinesis-block micronucleus (CBMN) assay. Urinary 1-hydroxypyrene (1-OHP) levels were measured as the internal dose of PAHs exposure. Two single nucleotide polymorphisms(SNPs) in MTHFR gene, including C677T, A1298C were detected by PCR-RFLP. The MTHFR haplotypes were estimated by Bayesian statistical method with the software of PHASE Version 2.1. The associations between haplotype pairs and CBMN were assessed by analysis of covariance in the coke-oven workers and controls.


RESULTS
The variant allele frequencies for MTHFRC677T and A1298C were 0.56 and 0.16 respectively, which consistent with Hardy-Weinberg equilibrium. There was linkage disequilibrium between the two SNPs (D' = 0.99) in this study. Four haplotypes were calculated by PHASE, in terms of 677T - 1298A, 677C-1298A, 677C-1298C and 677T-1298C, the frequencies were 0.555,0.279,0.163 and 0.003 respectively. In coke-oven workers, the frequencies of total micronucleus of non-677C-1298A/677C-1298A haplotype pair was significantly higher than 677C-1298A/677C-1298A (1.00 +/- 0.67 vs 0.60 +/- 0.41, P = 0.04). The frequencies of total micronucleus of 677T-1298A/677T-1298A haplotype pair was significantly higher than 677C-1298A/677C-1298A (1.08 +/- 0.71 vs 0.60 +/- 0.41, P = 0.04). In coke-oven workers, the frequencies of total micronucleus among the different SNPs were not significant differences, either in the controls.


CONCLUSIONS
The haplotypes of MTHFR gene might be one genetic susceptibility factors of PAH induced chromosomal damage in coke-oven workers.
Sun
Yao-feng
YF
Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing.
Dai
Yu-fei
YF
Cheng
Juan
J
Leng
Shu-guang
SG
D000395:Air Pollutants, Occupational / Q000633:toxicity; D016022:Case-Control Studies; D003077:Coke / Q000633:toxicity*; D004249:DNA Damage; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011721:Pyrenes / Q000032:analysis
D000395:Air Pollutants, Occupational; D003077:Coke; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C033146:1-hydroxypyrene