title: The T-786C NOS3 polymorphism in Alzheimer's disease: association and influence on gene expression.
abstract: A common single nucleotide polymorphism (SNP), consisting in a T-->C transition (T-786C) in endothelial nitric oxide synthase (NOS3), has been reported to be associated with vascular pathologies, but no information are available on a possible association with AD. T-786C genotype was determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) assay in an Italian population of 432 AD patients compared with 360 healthy controls, matched for ethnic background, age and gender. Peripheral blood mononuclear cells (PBMC) from 22 subjects (11 AD and 11 controls) carrying different genotypes were isolated. Total RNA was extracted and analyzed by real-time PCR. No significant differences either in allelic or genotypic frequencies of the T-786C polymorphism between AD and normal population were observed, even stratifying AD patients by age at onset, gender, or ApoE status. However, expression of NOS3 in PBMC seems to be influenced by the presence of the C mutated allele, as demonstrated by a tendency towards a decrease in mRNA levels in C carriers, assessed by real-time PCR assay. This effect was observed both in patients and controls, independently from the cognitive impairment, and is likely to be dose-dependent, being mostly evident in CC homozygous. In conclusion, the T-786C SNP does not seem to be a risk factor for sporadic AD, but its presence correlates with a trend toward lower NOS3 expression rate, possibly exerting a beneficial effect in AD by contributing to lower oxidative damage.
authors.affiliation: Department of Neurological Sciences, "Dino Ferrari" Center and CEND, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Carlo
authors.initials: C
authors.lastname: Lovati
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Diego
authors.initials: D
authors.lastname: Scalabrini
authors.forename: Claudio
authors.initials: C
authors.lastname: Mariani
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III