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Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease.
Eur J Neurol. 2011 May; 18(5):756-65.EJ

Abstract

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 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 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.

Authors+Show Affiliations

Division of Epidemiology, Department of Health Research and Policy, School of Medicine, Stanford University, Stanford, CA 94305-5405, USA. rpopat@stanford.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

21281405

Citation

Popat, R A., et al. "Coffee, ADORA2A, and CYP1A2: the Caffeine Connection in Parkinson's Disease." European Journal of Neurology, vol. 18, no. 5, 2011, pp. 756-65.
Popat RA, Van Den Eeden SK, Tanner CM, et al. Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease. Eur J Neurol. 2011;18(5):756-65.
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., & Nelson, L. M. (2011). Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease. European Journal of Neurology, 18(5), 756-65. https://doi.org/10.1111/j.1468-1331.2011.03353.x
Popat RA, et al. Coffee, ADORA2A, and CYP1A2: the Caffeine Connection in Parkinson's Disease. Eur J Neurol. 2011;18(5):756-65. PubMed PMID: 21281405.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease. AU - Popat,R A, AU - Van Den Eeden,S K, AU - Tanner,C M, AU - Kamel,F, AU - Umbach,D M, AU - Marder,K, AU - Mayeux,R, AU - Ritz,B, AU - Ross,G W, AU - Petrovitch,H, AU - Topol,B, AU - McGuire,V, AU - Costello,S, AU - Manthripragada,A D, AU - Southwick,A, AU - Myers,R M, AU - Nelson,L M, Y1 - 2011/01/31/ PY - 2011/2/2/entrez PY - 2011/2/2/pubmed PY - 2012/3/17/medline SP - 756 EP - 65 JF - European journal of neurology JO - Eur J Neurol VL - 18 IS - 5 N2 - 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 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 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. SN - 1468-1331 UR - https://www.unboundmedicine.com/medline/citation/21281405/Coffee_ADORA2A_and_CYP1A2:_the_caffeine_connection_in_Parkinson's_disease_ L2 - https://doi.org/10.1111/j.1468-1331.2011.03353.x DB - PRIME DP - Unbound Medicine ER -