慢性锰中毒易感性与基因多态性的病例对照研究

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。

Genetic polymorphism and susceptibility to occupational chronic manganism: a case-control study

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 Hha I restriction fragment length polymorphism (RFLP). The substitution of 609(C-T) at exon 6 of DT-diaphroase gene was analyzed by PCR combined Hinf I 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 variant of CYP2D6L gene and occupational manganism. These results suggest that the CYP2D6 gene might be one of the susceptibility genes for Mn-induced neurotoxicity. The allele and genotype frequencies of NQO1 gene were similar in the manganism cases and control subjects. CONCLUSION: It is possible that CYP2D6 gene may be a valuable susceptibility biomarker responded to Mn-induced central nervous system disorders in workers exposed to manganese.