NO ASSOCIATION BETWEEN AN INTRONIC POLYMORPHISM IN THE PRESENILIN-1 GENE AND ALZHEIMERS-DISEASE

Mutations in the presenilin-1 (PS-I) gene are believed to be responsib le for the majority of familial early-onset Alzheimer's disease (AD). The finding of an intronic polymorphism in the PS-I gene prompted an i nvestigation into its relevance in AD. An association between homozygo sity for the most common allele (allele 1) in this intronic polymorphi sm and late-onset AD has been shown and has been confirmed by others t hough some studies do not support these findings. We genotyped a large series of sporadic AD cases (n = 120) and age-matched controls (n = 1 08) for this intronic polymorphism. We then compared both the frequenc y of allele 1 and allele 1 homozygosity between the AD group as a whol e and in early-onset (n = 26) and late-onset (n = 94) groups with age- matched control groups (n = 29 and n = 79, respectively). No increase in the frequency or homozygosity of allele 1 in either the AD group as a whole, or when divided into late-and early-onset cases was found. I ncreases in the frequency of allele 1 homozygotes and in the number of non-apolipoprotein E epsilon 4 carrying allele 1 homozygotes/heterozy gotes was demonstrated in the early-onset AD cases although these valu es did not reach significance. We conclude that there is no relationsh ip between this intronic polymorphism in the PS-1 gene and AD in the h omogenous population genotyped in this study. (C) 1997 Elsevier Scienc e Ireland Ltd.