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Association between Alzheimer's disease and the NOS3 gene
Author(s) -
Dahiyat Mohammed,
Cumming Alastair,
Harrington Charles,
Wischik Claude,
Xuereb John,
Corrigan Frank,
Breen Gerome,
Shaw Duncan,
St Clair David
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199910)46:4<664::aid-ana18>3.0.co;2-j
Subject(s) - apolipoprotein e , locus (genetics) , alzheimer's disease , genetics , biology , gene , nitric oxide , medicine , endocrinology , disease
Alzheimer's disease (AD) is the most common form of neurodegenerative disorder of later life. Genetic studies have demonstrated that the apolipoprotein E (ApoE) gene is an important susceptibility locus; however, other environmental and genetic factors operating alone or in combination with ApoE must also be involved. Among candidate genes that may contribute to this residual risk is the endothelial nitric oxide synthase ( NOS3 ) gene. NO release from vascular endothelium accounts in large part for endothelium‐derived relaxing factor bioactivity. Abnormalities of cerebral small vessels occur early in AD, and it has been demonstrated recently that β‐amyloid interacts with endothelial cells in blood vessels to produce an excess of superoxide radicals. We have genotyped 122 cases of early‐onset AD (EOAD) and 317 cases of late‐onset AD (LOAD) as well as 392 controls for a common structural polymorphism Glu/Asp at codon 298 in the NOS3 gene. We find a highly significant enrichment for Glu/Glu homozygotes in LOAD compared with controls. The effect appears to be independent of ApoE status. NOS3 may be a new genetic risk factor for LOAD.