Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Drug Metab Pharmacokinet. 2013;28(2):138-43. doi: 10.2133/dmpk.dmpk-12-rg-075. Epub 2012 Sep 11.
It has been suggested that P-glycoprotein (P-gp), the product of multidrug resistance 1 (MDR1) gene, regulates the brain entry of various xenobiotics. Impaired function of P-gp may be associated with an increased risk of Parkinson's disease (PD). The aim of this study was to investigate the impact of a MDR1 C3435T polymorphism on PD risk alone or in combination with environmental factors. A total of 238 patients with PD and 368 controls were genotyped for the MDR1 C3435T polymorphism. Subjects with the TT genotype of the C3435T polymorphism showed a nonsignificantly increased risk of PD [odds ratio (OR)=1.49, 95% confidence interval (CI)=0.85-2.25] compared with those with the CC genotype. A gene-environment interaction was suggested, with a combination of at least one T allele and ever drinking conferring significantly higher risk (OR=1.83, 95% CI=1.07-3.15, p=0.029), compared with the CC genotype and never drinking. No significant interaction of smoking or occupational pesticide use with the C3435T polymorphism was observed. Our results suggest that the C3435T polymorphism may not play an important role in PD susceptibility in Japanese. Evidence of an interaction between the C3435T polymorphism and alcohol consumption was suggested.
有人提出，多药耐药基因 1（MDR1）产物 P-糖蛋白（P-gp）调节各种外源性物质进入大脑。P-gp 功能受损可能与帕金森病（PD）风险增加有关。本研究旨在单独或结合环境因素研究 MDR1 C3435T 多态性对 PD 风险的影响。对 238 名 PD 患者和 368 名对照进行 MDR1 C3435T 多态性基因分型。与 CC 基因型相比，C3435T 多态性 TT 基因型的受试者 PD 风险无显著增加[比值比（OR）=1.49，95%置信区间（CI）=0.85-2.25]。提示存在基因-环境相互作用，与 CC 基因型和从不饮酒相比，至少携带一个 T 等位基因且有饮酒史的个体患 PD 的风险显著更高（OR=1.83，95% CI=1.07-3.15，p=0.029）。未观察到吸烟或职业性农药使用与 C3435T 多态性之间存在显著的相互作用。我们的结果表明，C3435T 多态性在日本人群中可能对 PD 易感性没有重要作用。提示 C3435T 多态性与饮酒之间存在相互作用的证据。
