DEBRISOQUINE HYDROXYLASE GENE POLYMORPHISM FREQUENCIES IN PATIENTS WITH AMYOTROPHIC-LATERAL-SCLEROSIS

Using PCR and restriction digest analysis, the frequencies of the vari ant cytochrome P450 debrisoquine hydroxylase CYP2D6 al leles CYP2D6(A) and CYP2D6(B) were investigated in 50 patients with amyotrophic later al sclerosis (ALS) and 13 patients with ALS and frontotemporal dementi a (FTD) and compared to those frequencies in patients with FTD alone a nd Alzheimer's disease (AD). The CYP2D6(T) allelic frequency was also assessed in ALS and ALS + FTD. Although the frequency of a poor metabo lizer genotype was not increased in any disease group, there was a sig nificant 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 'g ain of function' imposed by the mutation or reflecting linkage disequi librium to a nearby susceptibility gene.