Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2.
Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2.
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DOI：
10.1159/000450855
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发表时间：
2016
影响因子：
5.7
通讯作者：
Ritz B
中科院分区：
文献类型：
--
作者：
Chuang YH;Lill CM;Lee PC;Hansen J;Lassen CF;Bertram L;Greene N;Sinsheimer JS;Ritz B
据报道，喝含咖啡因的咖啡可以预防帕金森病（PD）。咖啡因是一种腺苷A2 A受体（由基因ADORA 2A编码）拮抗剂，可增加多巴胺能神经传递，细胞色素P450 1A 2（基因：CYP 1A 2）代谢咖啡因，因此ADORA 2A和CYP 1A 2的基因多态性可能影响咖啡摄入对PD风险的影响。在丹麦进行的一项基于人群的病例对照研究（PASIDA）（1，556例PD患者和1，606例出生年份和性别匹配的对照）中，我们使用logistic回归模型分别评估了所有受试者以及偶发和流行PD病例的终生咖啡摄入量与ADORA 2A和CYP 1A 2三种多态性之间的相互作用。我们还进行了一项荟萃分析，将我们的结果与以前的研究结果相结合。我们估计了ADORA 2A rs 5760423与事件中重度与轻度咖啡消耗的统计学显著相互作用（OR相互作用=0.66 [0.46-0.94]，p=0.02），但不是普遍PD。我们没有观察到CYP 1A 2 rs762551和rs 2472304在偶发或流行PD中的相互作用。在荟萃分析中，PD与每日咖啡摄入量的相关性在ADORA 2A和CYP 1A 2变异等位基因携带者中最强。我们证实了先前报告的结果，该报告描述了ADORA 2A和CYP 1A 2多态性与咖啡消费之间的相互作用。我们的研究结果还表明，幸存者偏见可能会影响研究结果，招募流行的PD病例。
Drinking caffeinated coffee has been reported to protect against Parkinson’s disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine, thus gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. In a population-based case control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and sex- matched controls), we assessed interactions between lifetime coffee consumption and three polymorphisms in ADORA2A and CYP1A2 for all subjects and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction=0.66 [0.46–0.94], p=0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2. We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enrol prevalent PD cases.