Division of Epidemiology, Department of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA 94305-5405, USA.
Eur J Neurol. 2011 May;18(5):756-65. doi: 10.1111/j.1468-1331.2011.03353.x. Epub 2011 Jan 31.
In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association.
Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression.
Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5' variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04).
In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms.
在 1-甲基-4-苯基-1,2,3,6-四氢吡啶帕金森病（PD）动物模型中，咖啡因通过阻断腺苷受体 A2A（ADORA2A）来保护神经元。咖啡因主要由细胞色素 P450 1A2（CYP1A2）代谢。我们的目的是研究 ADORA2A 和 CYP1A2 多态性是否与 PD 风险相关，或者是否能改变咖啡因与 PD 的关联。
美国帕金森病流行病学和遗传关联研究（PEGASUS）包括五个基于人群的病例对照研究。一个实验室在 1325 例 PD 病例和 1735 名年龄和性别匹配的对照中，对四个 ADORA2A 和三个 CYP1A2 多态性进行了基因分型。关于咖啡因（咖啡）消费和其他生活方式因素的信息来自于结构化的面对面或电话访谈。使用逻辑回归估计比值比（OR）和 95%置信区间（CI）。
两个 ADORA2A 多态性与 PD 风险呈负相关-rs71651683，一个 5' 变体（调整后的等位基因 OR = 0.51，95%CI 0.33-0.80，置换调整后的 P = 0.015）和 rs5996696，一个启动子区域变体（与 AA 野生型基因型相比，AC 和 CC 基因型的调整后的 OR 分别为 0.76（95%CI 0.57-1.02）和 0.37（95%CI 0.13-1.01）（趋势的置换调整后的 P = 0.04）。CYP1A2 多态性与 PD 风险无关；然而，在 rs762551（P(交互) = 0.05）或 rs2470890（P(交互) = 0.04）两种变体等位基因纯合的受试者中，咖啡与 PD 的关联最强。
在这项联合研究中，两个 ADORA2A 多态性与 PD 风险呈负相关，但与咖啡因摄入的相互作用证据较弱。相比之下，在 CYP1A2 多态性纯合携带者中，咖啡与 PD 的关联在咖啡因代谢缓慢的人群中最强。
