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Lookup NU author(s): Dr Christopher Morris, Dr Louise Allan, Dr Elise Rowan, Dr Michael FirbankORCiD, Professor Gary Ford, Professor Rose Anne Kenny, Professor John O'Brien, Professor Raj KalariaORCiD
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Stroke is a major risk factor for the development of dementia in the elderly. It is unclear which genes influence risk of delayed dementia after stroke. We tested a single nucleotide polymorphism (SNP) in endothelial nitric oxide synthase (NOS3) gene at codon 298 (single-nucleotide polymorphism rs1799983; p.Asp298Glu) in a cohort of 355 older (>75 years) stroke survivors, who had detailed cognitive assessments from 3 months poststroke, i.e., baseline when the patients were free of dementia and subsequently at annual intervals. Of these, 253 participants were genotyped for polymorphisms in NOS3 and apolipoprotein E (APOE). Our analysis showed that homozygosity for NOS3 TT rather than the GT or GG genotype was a significant factor in the development of dementia. The presence of TT genotype increased risk of incident dementia compared with GG genotype; hazard ratio, 3.14 (95% confidence interval, 1.64–5.99; p = 0.001). We hypothesize that this may be mediated by reduction of nitric oxide production and cerebral perfusion. Our findings, if replicated widely, have implications for treatments to ameliorate cognitive decline in stroke survivors.
Author(s): Morris CM, Ballard CG, Allan L, Rowan E, Stephens S, Firbank MJ, Ford GA, Kenny RA, O'Brien JT, Kalaria RN
Publication type: Article
Publication status: Published
Journal: Neurobiology of Aging
Year: 2011
Volume: 32
Issue: 3
Pages: 554.e1-554.e6
Print publication date: 05/08/2010
ISSN (print): 0197-4580
ISSN (electronic): 1558-1497
Publisher: Elsevier
URL: http://dx.doi.org/10.1016/j.neurobiolaging.2010.06.012
DOI: 10.1016/j.neurobiolaging.2010.06.012
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