title: Debrisoquine hydroxylase gene polymorphism frequencies in patients with amyotrophic lateral sclerosis.
abstract: Using PCR and restriction digest analysis, the frequencies of the variant cytochrome P450 debrisoquine hydroxylase CYP2D6 alleles CYP2D6(A) and CYP2D6(B) were investigated in 50 patients with amyotrophic lateral sclerosis (ALS) and 13 patients with ALS and frontotemporal dementia (FTD) and compared to those frequencies in patients with FTD alone and Alzheimer's disease (AD). The CYP2D6(T) allelic frequency was also assessed in ALS and ALS + FTD. Although the frequency of a poor metabolizer genotype was not increased in any disease group, there was a significant increase in the frequency of the CYP2D6(B) allele in the ALS patient group. This suggests that possession of a CYP2D6(B) allele may be a risk factor for the development of ALS, possibly conferring a 'gain of function' imposed by the mutation or reflecting linkage disequilibrium to a nearby susceptibility gene.
authors.affiliation: Department of Pathological Sciences, University of Manchester, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Siddons
authors.forename: S M
authors.initials: SM
authors.lastname: Pickering-Brown
authors.forename: D M
authors.initials: DM
authors.lastname: Mann
authors.forename: F
authors.initials: F
authors.lastname: Owen
authors.forename: P N
authors.initials: PN
authors.lastname: Cooper
mesh_terms: D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6