Association between caffeine intake and risk of Parkinson's disease among fast and slow metabolizers.
BACKGROUND
Cytochrome P450 1A2 (CYP 1A2) is responsible for more than 90% of caffeine clearance. A polymorphic variant of CYP1A2 (-163C>A) (rs762551) is associated with high CYP1A2 inducibility. Both caffeine and its main metabolite, paraxanthine, may be neuroprotective. The association between caffeine intake and risk of Parkinson's disease (PD) in fast and slow caffeine metabolizers has not been compared.


OBJECTIVE
In a case-control study, we analyzed the relationship between caffeine intake and risk of PD in both fast and slow caffeine metabolizers.


METHODS
All the study participants were recruited prospectively, and interviewed for information on the amount and duration of caffeine intake. Genotyping of the CYP1A2 variant was carried out using the allelic discrimination method.


RESULTS
Out of 1000 participants who were initially screened, 886 consisting of 418 PD and 468 race, sex and age matched controls were included. No evidence existed to suggest any association between CYP1A2 and the onset of PD (P=0.08). A significant association was seen between caffeine intake and the onset of PD (P=2.01x10(-5)), with the odds ratio for moderate and high drinkers at 0.71 [95% confidence interval (CI): 0.50-1.00] and 0.47 (95% CI: 0.34-0.65), respectively against the low drinkers. Multivariate analysis revealed no evidence of any interaction effects of caffeine with CYP1A2 (P=0.956).


CONCLUSIONS
The association between caffeine intake and risk of PD was similarly observed in both fast and slow caffeine metabolizers, supporting experimental evidence in animal models that both caffeine and its major metabolite, paraxanthine, are neuroprotective.
Tan
Eng-King
EK
Departments of Neurology, Singapore General Hospital, Singapore. gnrtek@sgh.com.sg
Chua
Eva
E
Fook-Chong
Stephanie M
SM
Teo
Yik-Ying
YY
Yuen
Yih
Y
Tan
Louis
L
Zhao
Yi
Y
D000368:Aged; D002110:Caffeine / Q000009:adverse effects*; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003069:Coffee / Q000009:adverse effects; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
D000697:Central Nervous System Stimulants; D003069:Coffee; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2