CYP2D6 polymorphism in Parkinson's disease: The Rotterdam Study

The CYP2D6 polymorphism has been studied extensively in association with Parkinson's disease (PD), with no consistent results. Several explanations, such as differences in study design or bias in the selection of the control population, have been offered for these inconsistent results. We designed a case control study nested within a prospective population-based cohort study in which cases and controls were sampled from the same source population. To assess the significance of the CYP2D6 gene in PD, we investigated two mutant alleles, CYP2D6*3 and CYP2D6*4, associated with poor metabolism and the wild type allele in 80 patients with PD and 156 matched controls, frequency matched on age and gender. No differences between cases and controls were found for the poor metabolizer genotype. However, we found that in contrast to earlier reports, the CYP2D6*4 mutant allele frequency was lower in cases as compared to controls, albeit not statistically significant. Our result supports the hypothesis that the CYP2D6 gene is not a major gene responsible for PD.

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