Agúndez J A, Jiménez-Jiménez F J, Luengo A, Bernal M L, Molina J A, Ayuso L, Vázquez A, Parra J, Duarte J, Coria F
Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
Clin Pharmacol Ther. 1995 Mar;57(3):291-8. doi: 10.1016/0009-9236(95)90154-X.
The frequency of five cytochrome P450IID6 allelic variants was studied in deoxyribonucleic acid from 123 patients with Parkinson's disease and 150 healthy volunteers. This was achieved by the use of mutation-specific polymerase chain reaction and restriction fragment length polymorphism. The analyses of the CYP2D6 genotype revealed no evidence for a higher prevalence of poor metabolizers among patients with Parkinson's disease. However, increased frequency of patients with Parkinson's disease with the genotype CYP2D6wt/CYP2D6B was observed. This is attributable exclusively to subjects with early onset of the disease (28 to 49 years), with a relative risk ratio of 4.16 (95% confidence limits, 2.0 to 8.3; p < 0.0005). The subjects who had late-onset Parkinson's disease (> or = 50 years) had genotypes and CYP2D6 allele frequencies similar to the healthy subjects. This indicates that the oxidative polymorphism is related to early-onset but not to late-onset Parkinson's disease. A different influence of CYP2D6 genotype on the risk of development of Parkinson's disease is observed in Spaniards, compared with previous findings in British subjects. These results suggest the combined effect of environmental toxins and CYP2D6 in the cause of Parkinson's disease.
在123例帕金森病患者和150名健康志愿者的脱氧核糖核酸中研究了5种细胞色素P450IID6等位基因变体的频率。这是通过使用突变特异性聚合酶链反应和限制性片段长度多态性来实现的。对CYP2D6基因型的分析没有发现帕金森病患者中代谢不良者患病率更高的证据。然而，观察到帕金森病患者中CYP2D6wt/CYP2D6B基因型的频率增加。这完全归因于疾病早期发作（28至49岁）的受试者，相对风险比为4.16（95%置信区间，2.0至8.3；p<0.0005）。帕金森病晚期发作（≥50岁）的受试者的基因型和CYP2D6等位基因频率与健康受试者相似。这表明氧化多态性与早发性帕金森病有关，而与晚发性帕金森病无关。与之前在英国受试者中的发现相比，在西班牙人中观察到CYP2D6基因型对帕金森病发病风险的不同影响。这些结果表明环境毒素和CYP2D6在帕金森病病因中的联合作用。
