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- Title
Association of a Functional NOS1 Promoter Repeat with Alzheimer's Disease in the VITA Cohort.
- Authors
Reif, Andreas; Grünblatt, Edna; Herterich, Sabine; Wichart, Ildiko; Rainer, Michael K.; Jungwirth, Susanne; Danielczyk, Walter; Deckert, Jürgen; Tragl, Karl-Heinz; Riederer, Peter; Fischer, Peter
- Abstract
NO synthase, type I (NOS-I) has been suggested to play a role in the etiology of Alzheimer's disease (AD). The gene encoding NOS-I harbors at least nine alternative first exons; in the promoter region of exon 1f, a polymorphic repeat (NOS1 ex1f-VNTR) has been described which influences gene expression and neuronal transcriptome. We have shown that short alleles of this repeat are associated with AD. Here, we sought to further explore this finding by investigating a longitudinal cohort sample from the Vienna-Transdanube-Aging (VITA) study consisting of 606 subjects enrolled at the age of 75 (of these, genotypes were available for 574 subjects) and followed up for 60 months. The ex1f-VNTR risk genotype was associated with AD in the total sample and at the second follow-up. Thus, either long alleles of NOS1 ex1f-VNTR are protective against disease or conversely, short alleles predispose to earlier onset of disease. As demonstrated, ex1f-VNTR interacted with the apolipoprotein E ℇ4 risk allele (OR in the presence of both risk alleles 3.63; 95% CI: 1.45-9.12). These findings provide further evidence for an association of NOS1 with AD.
- Subjects
GENETICS of Alzheimer's disease; ETIOLOGY of diseases; GENETIC polymorphisms; GENE expression; AGING
- Publication
Journal of Alzheimer's Disease, 2011, Vol 23, Issue 2, p327
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2010-101491