Journal
NEUROBIOLOGY OF AGING
Volume 29, Issue 9, Pages 1359-1365Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2007.03.003
Keywords
Alzheimer's disease; genetics; polymorphism; neuronal nitric oxide synthase (NOS1); risk factor
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The gene encoding NOS-I (NOS]) displays a complex transcriptional regulation, with nine alternative first exons. Exon 1c and If are the most abundant forms in the brain. A functional single nucleotide polymorphism (SNP) in exon 1c and a polymorphism in exon If, consisting of a variable number of tandem repeats (VNTR) originating short (S) and long (L) alleles, were studied in 184 patients with Alzheimer's disease (AD) and 144 gender- and age-matched controls. No differences were found for the Ex1c G-84A. The Ex1f-VNTR S allele was significantly more common in AD (55% versus 44%, P=0.009, OR = 1.52) as was the S/S genotype (28% versus 14%, P=0.008; OR=2.37). The S allele showed a highly significant interaction with the ApoE epsilon 4 allele (OR: 10.83). Therefore, short alleles of the NOS1 exon If-VNTR are likely to be susceptibility factors for AD, and interact with the epsilon 4 allele to markedly increase the AD risk. (C) 2007 Elsevier Inc. All rights reserved.
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