Dr. Oesterheld's Comment: There is a major effort afoot to find associations between CYP polymorphisms and risk of disease. There is a polymorhism of CYP1A2 associated with increased CYP1A2 inducibility. This study was undertaken to find an association between this polymorphism and Parkinsonism. Although no such association was found in the study described below, there was an interesting association found between amount of caffeine intake and the onset of Parkinsonism.

Pharmacogenet Genomics. 2007 Nov;17(11):1001-5.

Association between caffeine intake and risk of Parkinson's disease among fast and slow metabolizers.

Tan EK, Chua E, Fook-Chong SM, Teo YY, Yuen Y, Tan L, Zhao Y.

INTRODUCTION

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).

CONCLUSION

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.

PMID: 18075470