title: Genotyping of CYP2D6 in Parkinson's disease.
abstract: Parkinson's disease is characterized by progressive degradation of dopaminergic neurons. Cytochrome P450 CYP2D6 enzyme is one of the most investigated and highly polymorphic isoforms, which metabolizes many drugs and is also involved in the metabolism of dopamine. Using allele-specific multiplex PCR, we genotyped 186 subjects for CYP2D6 *3, *4, *6, *7, and *8 alleles in order to estimate allelic, genotype and predicted phenotype frequencies in the 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 subgroups according to Hoehn and Yahr staging of the disease (HY), i.e. groups with 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 as "on-off" phenomenon and dyskinesia (both suggesting favorable response to therapy) were compared with a subgroup of patients showing no such response. The preliminary results of this study showed that only the prevalence of CYP2D6 *4 allele differed significantly between the PD patients and control 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 significance of p=0.095.
authors.affiliation: Clinical Institute of Chemistry, School of Medicine, University of Zagreb & Sestre milosrdnice University Hospital, Zagreb, Croatia. mario.stefanovic@zg.tel.hr
authors.forename: M
authors.initials: M
authors.lastname: Stefanović
authors.forename: E
authors.initials: E
authors.lastname: Topić
authors.forename: A M
authors.initials: AM
authors.lastname: Ivanisević
authors.forename: M
authors.initials: M
authors.lastname: Relja
authors.forename: M
authors.initials: M
authors.lastname: Korsić
mesh_terms: D000328:Adult; D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012306:Risk
chemical_list: D019389:Cytochrome P-450 CYP2D6