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慢性锰中毒易感性与基因多态性的病例对照研究 |
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郑玉新 何凤生 陈彪 潘祖飞 王忠旭 潘举升 周晓蓉
【摘要】 目的 探讨遗传因素与慢性职业性锰中毒的关系。方法 病例组为49名职业性锰中毒患者，来源于近15年来3个钢铁公司诊断的锰中毒病例，发病前为接触锰的冶炼工和电焊工；对照组为50名与病例组同车间、同工种、未发生锰中毒的工人，且年龄、性别、吸烟饮酒习惯和锰暴露时间等均相近。对细胞色素氧化酶P4502D6（CYP2D6）基因NQO1基因进行了分析。CYP2D6基因2938C-T的多态性应用PCR结合限制性内切酶（HhaⅠ酶）片断长度多态性（RFLP）进行分析；NQO1基因的第6外显子的609C-T多态性应用PCR结合HinfⅠ酶切的RFFP分析。结果 CYP2D6L等位基因频率在锰中毒工人和无中毒工人之间的差异有显著性，CYP2D6L基因型在锰中毒患者中的分布明显低于对照组，提示CYP2D6基因可能是与锰中毒有关的易感/耐受基因。未发现NQO1基因在两组间分布的差异有显著性。结论 本研究显示CYP2D6基因可能是锰致神经系统损害的易感性/耐受性生物标志物之一。
【关键词】 锰 中毒 细胞色素P-450CYP2D6 多态现象(遗传学)
Genetic Polymorphism and Susceptibility to Occupational Chronic Manganism: A Case-control Study ZHENG Yuxin*, HE Fengsheng, CHAN Piu, et al. *Institute of Occupational Medicine, Chinese Academy of Preventive Medicine, Beijing 100050
【Abstract】 Objective In a case-control study, the possible genetic factors relevance to occupational chronic manganism were investigated. Methods Forty-nine manganisms who were welders and ferromanganese smelters occupationally exposed to manganese dust and fume from three metallurgical industries, and fifty unrelated healthy control subjects who were working same workshops were recruited. The subjects were matched for sex, age, cigarette and alcohol intake. The manganese exposure duration was also matched in this case-control study. Genetic polymorphism of cytochrome P450 2D6L (CYP2D6L) gene and NAD(P)H: quinone oxidreductase (NQO1) genes from all subjects were investigated. The mutations of CYP2D6L gene located exon 6 were analyzed by a polymerase chain reaction (PCR)-based DNA amplification combined with HhaⅠ restriction fragment length polymorphism (RFLP). The substitution of 609C-T at exon 6 of DT-diaphroase gene was analyzed by PCR combined HinfⅠ RFLP. Results The frequency of polymorphic allels, a mutation of CYP2D6, was significantly lower in patients with manganism (16.3%) than that of the controls (29.0%). A significant association was also found between the homozygote vari[1] [2] 下一页
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