Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study.

Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study. Research Abstract Details 

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Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study. Abstract Text:

Gary F Mitchell,Chao-Yu Guo,Sekar Kathiresan,Ramachandran S Vasan,Martin G Larson,Joseph A Vita,Michelle J Keyes,Mitul Vyas,Christopher Newton-Cheh,Stacy L Musone,Amy L Camargo,Jared A Drake,Daniel Levy,Christopher J O'Donnell,Joel N Hirschhorn,Emelia J Benjamin,

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 approximately 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.

Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study. Publishing Authors By Initials

GF Mitchell,CY Guo,S Kathiresan,RS Vasan,MG Larson,JA Vita,MJ Keyes,M Vyas,C Newton-Cheh,SL Musone,AL Camargo,JA Drake,D Levy,CJ O'Donnell,JN Hirschhorn,EJ Benjamin,

For similar epidemiologic factors: sex factors research abstracts see: epidemiologic factors: sex factors research

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Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Hypertension

VOLUME: 49

Page Numbers: 1285-90

Journal Abbreviation: Hypertension

ISSN: 1524-4563

DAY: 2

MONTH: 04

YEAR: 2007

Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7906255

Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study. Keywords Mesh Terms:

KEYWORDS: Sex Factors

MESH TERMS: physiology

Chemical & Substance for Abstract: Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study. Information

Substance Name: Nitric Oxide Synthase Type III

Registry Number: EC 1.14.13.39

Grant and Affiliation Information for Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study.

AFFILIATION: Cardiovascular Engineering, Inc., Waltham, MA 02453, USA. GaryFMitchell@mindspring.com

Country: United States

AGENCY: United States NHLBI

GRANT: N01-HV28178

ACRONYM: HV

MEDLINETA: Hypertension

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