CYP2D6 polymorphism and Parkinson's disease susceptibility

Following the recent identification of multiple novel mutations and alleles of the cytochrome P450 CYP2D6 gene which cause decreased, increased, or ab sent enzyme activity. we re-examined the controversial hypothesis of a role of the CYP2D6 polymorphism in Parkinson's disease (PD) susceptibility. For this purpose, a strategy based on PCR-SSCP and RFLP analyses allowing the detection of all known CYP2D6 alleles was performed in DNA from 109 patient s with sporadic PD. This strategy was also applied to DNA from 68 members o f PD families including 18 affected and 50 unaffected members. Seventeen mu tations occurring alone or in various combination on 14 alleles of CYP2D6 h ave been identified in patients with sporadic PD. Moreover, 12 mutations an d nine alleles of the gene have been characterized in members of PD familie s. No significant difference was observed when the distribution of mutation s and alleles of CYP2D6 was compared between the PD patients and 514 contro l subjects previously analyzed using the same strategy. There was also no d ifference in the distribution of phenotypes predicted from genotypes betwee n both groups. In addition, when the distribution of CYP2D6 genotypes was c ompared, no difference between affected and unaffected members of PD famili es was observed. These data indicate that CYP2D6 polymorphism is not a susc eptibility factor to PD.