Debrisoquine hydroxylase gene polymorphism frequencies in patients with amyotrophic lateral sclerosis.

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.

The extent of amyloid deposition in brain in patients with Down's syndrome does not depend upon the apolipoprotein E genotype.

The extent of deposition of amyloid beta protein (A beta) was investigated in 20 elderly patients with Down's syndrome, using the end-specific monoclonal antibodies BC05 and BA27 to detect the presence of A beta 42(43) and A beta 40 (respectively), and related to apolipoprotein E (ApoE) genotype. No significant differences in the amount of A beta deposited in the brain, either as A beta 42(43) or A beta 40, were noted in patients possessing an ApoE E4 allele, compared to those without. Patients with an ApoE E4 allele in general died at an earlier age than those with only ApoE E3 alleles, the latter in turn being outlived by those with an ApoE E2 allele. In Down's syndrome therefore, ApoE may influence the timing of onset, or the rate of progression, of disease but without affecting the type or total amount of pathology accumulated.