Document Detail

Endothelium-dependent vasodilation in conduit and resistance vessels in relation to the endothelial nitric oxide synthase gene.
MedLine Citation:
PMID:  18463668     Owner:  NLM     Status:  MEDLINE    
Single nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (NOS3) gene have been related to endothelium-dependent vasodilation in either conduit or resistance arteries with divergent results. In the Prospective Study of the Vasculature in Uppsala Seniors study, 959 participants aged 70 (51% men) were evaluated with brachial artery ultrasound to assess flow-mediated vasodilation (FMD; reflecting conduit arteries) and invasive forearm technique with intrabrachial infusion of acetylcholine (endothelium-dependent vasodilation (EDV); reflecting resistance arteries). The 23 SNPs analysed by minisequencing captured >90% of the common genetic variation in the NOS3 gene, using the HapMap population of European ancestry (CEU) as reference. One SNP (Glu298Asp) was related to FMD (nominal P=0.0018), but not to EDV (nominal P=0.76) after adjustment for sex, systolic blood pressure, diastolic blood pressure, pulse rate, antihypertensive treatment, total cholesterol, high-density cholesterol, lipid-lowering medication, fasting glucose, antidiabetic medication, body mass index, current smoking and prior diagnosis of cardiovascular disease. This relation was significant in both men and women in sex-specific analyses, and remained significant after adjusting for multiple testing (empirical P=0.029 from bootstrap resampling). None of the constructed haplotypes were related to vasodilation. The Glu298Asp SNP in the NOS3 gene was related to endothelium-dependent vasodilation in conduit, but not in resistance arteries. This SNP has previously been related to coronary heart disease, and our findings should stimulate to replication and exploration of the association of NOS3 variation with endothelial function in other settings.
E Ingelsson; A-C Syvänen; L Lind
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-08
Journal Detail:
Title:  Journal of human hypertension     Volume:  22     ISSN:  0950-9240     ISO Abbreviation:  J Hum Hypertens     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-17     Completed Date:  2008-12-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8811625     Medline TA:  J Hum Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  569-78     Citation Subset:  IM    
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
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MeSH Terms
Brachial Artery / physiopathology*,  ultrasonography
Cardiovascular Diseases / genetics*,  physiopathology
DNA / genetics*
Endothelium, Vascular / metabolism,  physiopathology
Follow-Up Studies
Gene Frequency
Genetic Predisposition to Disease
Nitric Oxide Synthase Type III / genetics*
Polymorphism, Genetic*
Prospective Studies
Vascular Resistance / genetics*
Vasodilation / genetics*
Reg. No./Substance:
9007-49-2/DNA; EC protein, human; EC Oxide Synthase Type III

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