GENETIC-ANALYSIS OF THE CYP2D6 GENE IN PATIENTS WITH PARKINSONS-DISEASE

To further investigate the association between Parkinson's disease (PD ) and genetic polymorphism of the CYP2D6 gene, a mutant allele (CYP2D6 J) frequently observed in the Japanese population and related to EM/PM polymorphism (phenotypically, individuals are either extensive metabo lizers [EW] or poor metabolizers [PM] of debrisoquine) was investigate d. The CYP2D6J gene with a nucleotide substitution from C to T at posi tion 188 (the Hphl site in exon 1), which reduces CYP2D6 enzyme activi ty, was analyzed by polymerase chain reaction (PCR) and by digestion w ith Hphl, No significant relationship was observed between PD patients and controls for this mutation, This suggests that the EM/PM polymorp hism of CYP2D6 contributes little to the pathogenesis of PD, To furthe r study the molecular basis for the relationship between PD and CYP2D6 , the heterogeneity of CYP2D6 was investigated by combined genotype an alysis of the two mutant CYP2D6 genes (ie, CYP2D6J, the Hphl site muta tion in exon 1, and CYP2D6L, the Hhal site mutation in exon 6). Althou gh some characteristic patterns of the combined genotypes were observe d in both PD patients and controls, a strong association between the h eterogeneity of the CYP2D6 gene and PD was not shown by combined genot ype analysis. Copyright (C) 1998 by W.B. Saunders Company.