亚甲基四氢叶酸还原酶基因单体型与焦炉作业工人染色体损伤易感性的关系  

Association between methylenetetrahydrofolate reductase gene haplotypes and the susceptibility of chromosomal damage in coke-oven workers

作　　者：孙耀峰[1] 戴宇飞[1] 程娟[1] 冷曙光[1] 牛勇[1] 潘祖飞[2] 郑玉新[1] 

机构地区：[1]中国疾病预防控制中心职业卫生与中毒控制所,北京100050 [2]辽宁省本溪钢铁集团有限责任公司劳动卫生研究所

出　　处：《卫生研究》2006年第4期387-390,共4页Journal of Hygiene Research

基　　金：国家973计划资助项目(No.2002CB512903);国家自然科学基金资助项目(No.30400348)

摘　　要：目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与焦炉作业工人染色体损伤易感性的关系。方法选取140名焦炉工和66名医护人员作为研究对象,采用胞质分裂阻滞微核实验评价个体染色体损伤水平,测定尿中1-羟基芘浓度反映多环芳烃暴露内剂量,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析MTHFR基因两个单核苷酸多态性(SNP)位点(C677T、A1298C),利用PHASE2·1软件经Bayesian法计算单体型。校正年龄、性别和尿1-羟基芘水平,用协方差分析比较MTHFR不同基因型或单体型之间外周血淋巴细胞微核率的差异。结果研究对象中MTHFRC677T和A1298C两个变异等位基因频率分别为0·56和0·16,其分布均符合Hardy-Weinberg平衡。本研究中MTHFR基因这两个SNPs存在连锁不平衡关系(D’=0·99),研究对象中有四种单体型677T-1298A、677C-1298A、677C-1298C和677T-1298C,其频率分别为0·555、0·279、0·163和0·003。在焦炉工组,非677C-1298A/677C-1298A单体型对的微核率高于677C-1298A/677C-1298A,差异有显著性(1·00±0·67vs0·60±0·41,P=0·04),其中677T-1298A/677T-1298A单体型对微核率高于677C-1298A/677C-1298A,差异有显著性(1·08±0·71vs0·60±0·41,P=0·04)。在焦炉工组和对照组中,未发现上述两个SNPs与微核率之间显著关联。结论MTHFR基因单体型可能是影响焦炉工染色体损伤的遗传易感性因素之一。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 PCRRFLP. 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 t 0.67 vs 0.60 t 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. Conclusion The haplotypes of MTHFR gene might be one genetic susceptibility factors of PAH induced chromosomal damage in coke-oven workers.

关 键 词：亚甲基四氢叶酸还原酶 单体型 微核率 

分 类 号：R135.12[医药卫生—劳动卫生]