Sun Yao-feng, Dai Yu-fei, Cheng Juan, Leng Shu-guang
Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing.
Wei Sheng Yan Jiu. 2006 Jul;35(4):387-90.
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).
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.
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.
The haplotypes of MTHFR gene might be one genetic susceptibility factors of PAH induced chromosomal damage in coke-oven workers.
探讨多环芳烃（PAHs）暴露焦炉工人中甲基四氢叶酸还原酶（MTHFR）基因变异与外周血淋巴细胞染色体损伤水平的关系。
选取140名PAHs高暴露焦炉工人和66名非暴露对照者作为研究对象。采用胞质分裂阻滞微核（CBMN）试验检测外周淋巴细胞染色体损伤。测定尿中1-羟基芘（1-OHP）水平作为PAHs暴露的内剂量。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测MTHFR基因的两个单核苷酸多态性（SNP），即C677T、A1298C。利用PHASE 2.1软件通过贝叶斯统计方法估计MTHFR单倍型。通过协方差分析评估焦炉工人和对照者中单倍型对与CBMN的关联。
MTHFRC677T和A1298C的变异等位基因频率分别为0.56和0.16，符合哈迪-温伯格平衡。本研究中两个SNP之间存在连锁不平衡（D' = 0.99）。PHASE计算出4种单倍型，分别为677T - 1298A、677C-1298A、677C-1298C和677T-1298C，频率分别为0.555、0.279、0.163和0.003。在焦炉工人中，非677C-1298A/677C-1298A单倍型对的总微核频率显著高于677C-1298A/677C-1298A（1.00±0.67 vs 0.60±0.41，P = 0.04）。677T-1298A/677T-1298A单倍型对的总微核频率显著高于677C-1298A/677C-1298A（1.08±0.71 vs 0.60±0.41，P = 0.04）。在焦炉工人中，不同SNP间的总微核频率无显著差异，对照者中也是如此。
MTHFR基因单倍型可能是PAHs诱导焦炉工人染色体损伤的遗传易感因素之一。
