DEBRISOQUINE HYDROXYLASE GENE POLYMORPHISM IN FAMILIAL PARKINSONS-DISEASE

Recent molecular genetic studies of the cytochrome P-450 system enzyme CYP2D6, which hydroxylates debrisoquine, have indicated an excess of mutant alleles in patients with Parkinson's disease compared with cont rols. This indicates that the CYP2D6 locus confers genetic susceptibil ity to Parkinson's disease. CYP2D6 polymorphism has been investigated in 48 patients with familial Parkinson's disease, from 22 families, an d 88 of their unaffected relatives. An excess of CYP2D6 mutant alleles in patients compared with healthy relatives was found only in subject s over the age of 60 years, presumably reflecting the age related prev alence of this disease. There was no difference in distribution of gen otypes, however, between sib pairs concordant or discordant for Parkin son's disease. Linkage analysis, exclusively with affected family memb ers, yielded negative led scores. These data indicate that the CYP2D6 locus is not the major determinant of genetic susceptibility in famili al Parkinson's disease.