Publication:

NOS3 gene rs1799983 polymorphism and incident dementia in elderly stroke survivors (2011)

Author(s): Morris CM, Ballard CG, Allan L, Rowan E, Stephens S, Firbank MJ, Ford GA, Kenny RA, O'Brien JT, Kalaria RN

    Abstract: 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.

      • Date: 05-08-2010
      • Journal: Neurobiology of Aging
      • Volume: 32
      • Issue: 3
      • Pages: 554.e1-554.e6
      • Publisher: Elsevier
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: APOE gene; Cerebral ischemia; Dementia; Cognitive impairment; NOS3 gene; Stroke; Vascular dementia

      Staff

      Professor Gary Ford
      Jacobson Chair of Clinical Pharmacology

      Professor Raj Kalaria
      Professor of Cerebrovascular Pathology (Neuropathology)

      Dr Christopher Morris
      Senior Lecturer

      Professor John O'Brien
      Strategic Research Advisor