NOS3 gene rs1799983 polymorphism and incident dementia in elderly stroke survivors.
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.
Morris
Christopher M
CM
Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
Ballard
Clive G
CG
Allan
Louise
L
Rowan
Elise
E
Stephens
Sally
S
Firbank
Michael
M
Ford
Gary A
GA
Kenny
Rose Anne
RA
O'Brien
John T
JT
Kalaria
Raj N
RN
D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D015331:Cohort Studies; D003704:Dementia / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D052250:Nitric Oxide Synthase Type III; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020521:Stroke / Q000150:complications*; D013534:Survival
D001057:Apolipoproteins E; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III