title: Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2.
abstract: Drinking caffeinated coffee has been reported to provide protection 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 gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 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 [95% CI 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 enroll prevalent PD cases.
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), USA.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Chuang
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lill
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Lee
authors.forename: Johnni
authors.initials: J
authors.lastname: Hansen
authors.forename: Christina F
authors.initials: CF
authors.lastname: Lassen
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.forename: Naomi
authors.initials: N
authors.lastname: Greene
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
mesh_terms: D000368:Aged; D003069:Coffee; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D003718:Denmark; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D012307:Risk Factors
chemical_list: D003069:Coffee; D043705:Receptor, Adenosine A2A; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2