Absence of effect of seven functional mutations in the CYP2D6 gene in Parkinson's disease

The reduction or loss of cytochrome P450 enzyme activity as a result of mut ations in the CYP2D6 gene has been suggested as a risk factor for Parkinson 's disease (PD). Conflicting, results among reported studies of the prevale nce of mutations among patients with PD suggested a more comprehensive geno typing and an analysis of the interactions with other suspected risk factor s and family history. We determined the frequency of seven CYP2D6 mutations among 109 patients with PD and 110 control subjects. Family history of PD, age of onset, exposure to pesticides or herbicides, and well-water consump tion were obtained for all cases. There was no significant difference in fr equency between patients with PD and control subjects for any mutant allele and no significant association with family history, onset age, or environm ental exposures. We sought to increase the power of our study by combining reports from the literature, choosing allele frequencies as the most inform ative measure. Although we found variability in reported allele frequencies for control subjects that made a metaanalysis problematic, summing all rep orts demonstrated no difference in CYP2D6 mutation frequency between patien ts with PD and control subjects. This comprehensive study of CYP2D6 mutatio ns demonstrates that other genes or shared environmental exposures account for the familial risk of PD.