Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson’s disease
Year: 2011
Type: article
Study design: Observational Study
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.
Source: European Journal of Neurology
Institutions: Stanford Medicine, Stanford University, Kaiser Permanente, Parkinson's Institute and Clinical Center, National Institutes of Health, National Institute of Environmental Health Sciences, Columbia University, University of California, Los Angeles, VA Pacific Islands Health Care System, Pacific Health Research and Education Institute, University of California, Berkeley, HudsonAlpha Institute for Biotechnology
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G110746662, G1507381378, G1723876641, G1807399734, G1850600219, CASE CONTROL/STUDY OF PARKINSONS DISEASE IN THE ELDERLY, Environmental, Genetic and Cellular Determinants of PD, Pesticides And Parkinson s Disease In The Agricultural Health Study, HONOLULU HEART PROGRAM, Epidemiology of Dementia In An Urban Community, Environmental and Genetic Risks for Parkinson's Disease, Parkinson's Diseases Susceptibility Genes and Pesticides, G4618563795, G585214908, G6465133350, G673202034, G7192843469, Gene-Occupational Exposure Interaction in P D, G8158392652, Environmental Exposures, Host Factors and Human Disease
OpenAlex ID: W2124900584