Genotyping of CYP2D6 in Parkinson's disease

Parkinson's disease is characterized by progressive degradation of dopamine rgic: neurons. Cytochrome P450 CYP2D6 enzyme is one of the most investigate d and highly polymorphic isoforms, which metabolizes many drugs and is also involved in the metabolism of dopamine. Using allele-specific multiplex PC R, we genotyped 186 subjects for CYP2D6 *3, *4, *6, *7, and *8 alleles in o rder to estimate allelic, genotype and predicted phenotype frequencies in t he control and patient groups, and to investigate the possible statistical difference between Parkinson's disease patients (n=41) and healthy controls (n=145). Parkinson's disease patients were further divided into two subgro ups according to Hoehn and Yahr staging of the disease (HY), i.e. groups wi th HY stage less than 2.5 (HY <2.5; n=27) and more than 2.5 (HY >2.5; n=14) . A subgroup of Parkinson's disease patients exhibiting side effects such a s "on-off" phenomenon and dyskinesia (both suggesting favorable response to therapy) were compared with a subgroup of patients showing no such respons e. The preliminary results of this study showed that only the prevalence of CYP2D6 *4 allele differed significantly between the PD patients and contro l group (20.7% vs. 11.0%; p=0.027; RR=2.1, 95%CI 1.113-3.994). In the HY >2 .5 subgroup, the CYP2D6*4 allelic difference was even greater (25.0% vs. 11 .0% in controls; p=0.062, RR=2.69, 95%CI 1.090-6.624). Genotype frequencies differed only in the HY >2.5 subgroup, however with a level of significanc e of p=0.095.