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Association of a functional NOS1 promoter repeat with Alzheimer's disease in the VITA cohort


Reif, A; Grünblatt, E; Herterich, S; Wichart, I; Rainer, M K; Jungwirth, S; Danielczyk, W; Deckert, J; Tragl, K H; Riederer, P; Fischer, P (2011). Association of a functional NOS1 promoter repeat with Alzheimer's disease in the VITA cohort. Journal of Alzheimer's Disease, 23(2):327-333.

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 ε4 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.

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 ε4 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:January 2011
Deposited On:04 Feb 2011 16:29
Last Modified:05 Apr 2016 14:43
Publisher:IOS Press
ISSN:1387-2877
Publisher DOI:10.3233/JAD-2010-101491
PubMed ID:21098972
Permanent URL: http://doi.org/10.5167/uzh-44566

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