Debrisoquine hydroxylase gene polymorphism in familial Parkinson's 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 controls. This indicates that the CYP2D6 locus confers genetic susceptibility to Parkinson's disease. CYP2D6 polymorphism has been investigated in 48 patients with familial Parkinson's disease, from 22 families, and 88 of their unaffected relatives. An excess of CYP2D6 mutant alleles in patients compared with healthy relatives was found only in subjects over the age of 60 years, presumably reflecting the age related prevalence of this disease. There was no difference in distribution of genotypes, however, between sib pairs concordant or discordant for Parkinson's disease. Linkage analysis, exclusively with affected family members, yielded negative lod scores. These data indicate that the CYP2D6 locus is not the major determinant of genetic susceptibility in familial Parkinson's disease.
Planté-Bordeneuve
V
V
University Department of Clinical Neurology (Neurogenetics and Movement Disorders Sections), Institute of Neurology, London, UK.
Davis
M B
MB
Maraganore
D M
DM
Marsden
C D
CD
Harding
A E
AE
D000367:Age Factors; D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008126:Lod Score; D016555:Matched-Pair Analysis; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D006113:United Kingdom / Q000453:epidemiology
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6