Present Address: HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL, USA.
Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson’s disease
Article first published online: 31 JAN 2011
© 2011 The Author(s). European Journal of Neurology © 2011 EFNS
European Journal of Neurology
Volume 18, Issue 5, pages 756–765, May 2011
How to Cite
Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., Kamel, F., Umbach, D. M., Marder, K., Mayeux, R., Ritz, B., Ross, G. W., Petrovitch, H., Topol, B., McGuire, V., Costello, S., Manthripragada, A. D., Southwick, A., Myers, R. M. and Nelson, L. M. (2011), Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson’s disease. European Journal of Neurology, 18: 756–765. doi: 10.1111/j.1468-1331.2011.03353.x
See editorial by Mellick and Ross, on page 671.
- Issue published online: 15 APR 2011
- Article first published online: 31 JAN 2011
- Received 15 June 2010 Accepted 27 October 2010
- adenosine receptor A2A;
- Parkinson’s disease;
Background and purpose: 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.
Methods: 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.
Results: 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 (Pinteraction = 0.05) or rs2470890 (Pinteraction = 0.04).
Conclusion: 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.