title: Association of a NOS1 promoter repeat with Alzheimer's disease.
abstract: The gene encoding NOS-I (NOS1) displays a complex transcriptional regulation, with nine alternative first exons. Exon 1c and 1f are the most abundant forms in the brain. A functional single nucleotide polymorphism (SNP) in exon 1c and a polymorphism in exon 1f, 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 1f-VNTR are likely to be susceptibility factors for AD, and interact with the epsilon 4 allele to markedly increase the AD risk.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Ospedale Maggiore Policlinico IRCCS, Milan, Italy. daniela.galimberti@unimi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Alexander
authors.initials: A
authors.lastname: Strobel
authors.forename: Sabine
authors.initials: S
authors.lastname: Herterich
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guidi
authors.forename: Diego
authors.initials: D
authors.lastname: Scalabrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*
chemical_list: D052248:Nitric Oxide Synthase Type I