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Vascular Stiffness and Genetic Variation at the Endothelial Nitric Oxide Synthase Locus: The Framingham Heart Study
Abstract
Arterial stiffness is a moderately heritable trait that is affected by alterations in the bioavailability of NO. Previous studies have found associations between variants in the gene for endothelial NO synthase ( NOS3 ) and arterial properties. We previously identified a linkage peak for forward pressure wave amplitude in the immediate vicinity of NOS3 . Therefore, we evaluated relations between arterial stiffness measures and common genetic variants at this locus. Eighteen single nucleotide polymorphisms capturing ≈90% of underlying common variation in NOS3 were genotyped in unrelated Framingham Heart Study participants (N=1157; 52.2% women; mean age: 62 years) with routinely ascertained tonometry data that provided 5 arterial phenotypes (forward and reflected pressure wave amplitude, central pulse pressure, carotid–femoral pulse wave velocity, and mean arterial pressure). In women but not men, the genotype for the common NOS3 missense mutation (Glu298Asp, rs1799983) was related to central pulse pressure (women: GG=53±0.9, GT=54±0.9, and TT=47±2.0 mm Hg, P =0.0047; men: GG=50±1.0, GT=49±0.9, and TT=47±1.8 mm Hg, P =0.30) and forward wave amplitude (women: GG=41±0.7, GT=42±0.7, and TT=38±1.6 mm Hg, P =0.029; men: GG=42±0.9, GT=41±0.8, and TT=39±1.5 mm Hg, P =0.47). The only other nominally significant sex-specific association in men but not women was between an intronic polymorphism (rs1800781) and reflected wave amplitude (women: AA=10.4±0.4, AG=11.1±0.6, and GG=8.9±2.2 mm Hg, P =0.50; men: AA=6.1±0.3, AG=7.3±0.5, and GG=11.3±2.3 mm Hg, P =0.014). After adjusting for multiple testing (18 polymorphisms and 5 phenotypes), these nominal associations were no longer significant. The present study was suggestive of modest relations between common genetic variants at the NOS3 locus and arterial stiffness.
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The rs1799983 polymorphism in NOS3 has been found to be associated with central pulse pressure in the Framingham Heart Study.
“and it has been found to be associated to central pulse pressure in the Framingham Heart Study [105]”
From Fenofibrate and metabolic syndrome (2010) · cites this paper as [105]
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Metadata
- Authors
- Mitchell, G. F., Guo, C.-Y., Kathiresan, S., Vasan, R. S., Larson, M. G., Vita, J. A., Keyes, M. J., Vyas, M., Newton-Cheh, C., Musone, S. L., Camargo, A. L., Drake, J. A., Levy, D., O’Donnell, C. J., Hirschhorn, J. N., & Benjamin, E. J.
- Affiliations
- Broad Institute (US)
- From Cardiovascular Engineering, Inc (G.F.M., M.V.), Waltham, Mass; National Heart, Lung, and Blood Institute’s Framingham Heart Study (S.K., M.G.L., R.S.V., C.-Y.G., M.J.K., C.N.-C., D.L., C.J.O., E.J.B.), Framingham, Mass; the Department of Mathematics and Statistics (M.J.K., M.G.L.), Evans Department of Medicine and Whitaker Cardiovascular Institute (R.S.V., J.A.V., E.J.B.), Boston University School of Medicine, Boston University, Mass; the Program in Medical and Population Genetics (S.K., C.N.-C...
- ORCID
- Venue
- Hypertension
- Published
- 2007-06
- Volume
- 49
- Issue
- 6
- Pages
- 1285-1290
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2092682483
- Cited by
- 38
- References
- 25
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2018: 3 · 2017: 1 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc25195-41-0-1, n01hv28178-12-0-0)
- National Heart, Lung, and Blood Institute (K-24-HL-04334, N01 HV28178, N01‐HC25195, U01HL066582, K24HL004334, HL71039, HL-70100, HL66582, R01HL070100, HL60040, R01HL060040, R01HL071039)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- arterial stiffness, endothelial nitric oxide synthase, NOS3, genetic association, single nucleotide polymorphisms, rs1799983, pulse wave velocity, central pulse pressure, pressure wave amplitude, sex differences, nitric oxide bioavailability, Framingham Heart Study, tonometry
- MeSH terms
- Aged, Arteries, Blood Pressure, Carotid Arteries, Elasticity, Female, Femoral Artery, Genotype, Humans, Genetic Linkage, Male, Middle Aged, Phenotype, Pulsatile Flow, Regional Blood Flow, Sex Factors, Cohort Studies, Mutation, Missense, Polymorphism, Single Nucleotide, Atherosclerosis, Nitric Oxide Synthase Type III
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