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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２９３８ＣＴ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６０９ＣＴ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。
Objective To investigate the relationship between genetic factors and chronic occupational manganese poisoning. Methods A total of 49 patients with occupational manganese poisoning were enrolled in this study. The patients were diagnosed as manganese poisoning by three steel companies in the past 15 years. Before the onset, manganese miners and welders were exposed. In the control group, 50 patients were in the same workshop as the case group, Similar types of workers, no manganese poisoning workers, and age, gender, smoking and drinking habits and exposure time are similar to manganese. The cytochrome oxidase P4502D6 (CYP2D6) gene NQO1 gene was analyzed. CYP2D6 gene 2938C T polymorphism by PCR and restriction endonuclease (Hha Ⅰ enzyme) fragment length polymorphism (RFLP) analysis; NQO1 gene exon 6 609C T polymorphism using PCR combined HinfI digested RFFP analysis. Results The frequency of CYP2D6L allele was significantly different between manganese poisoning workers and non-poisoning workers. The distribution of CYP2D6L genotype in patients with manganese poisoning was significantly lower than that of the control group, suggesting that CYP2D6 may be susceptible to manganese poisoning / Tolerant gene. No difference was found in the distribution of NQO1 between the two groups. Conclusions This study shows that the CYP2D6 gene may be one of the susceptible / tolerogenic biomarkers of manganese-induced nervous system damage.