TY - JOUR
T1 - Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus
T2 - The framingham heart study
AU - Mitchell, Gary F.
AU - Guo, Chao Yu
AU - Kathiresan, Sekar
AU - Vasan, Ramachandran S.
AU - Larson, Martin G.
AU - Vita, Joseph A.
AU - Keyes, Michelle J.
AU - Vyas, Mitul
AU - Newton-Cheh, Christopher
AU - Musone, Stacy L.
AU - Camargo, Amy L.
AU - Drake, Jared A.
AU - Levy, Daniel
AU - O'Donnell, Christopher J.
AU - Hirschhorn, Joel N.
AU - Benjamin, Emelia J.
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
KW - Epidemiology
KW - Medical genetics
KW - Nitric oxide synthase
KW - Pulse pressure
KW - Single nucleotide polymorphism
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U2 - 10.1161/HYPERTENSIONAHA.106.085266
DO - 10.1161/HYPERTENSIONAHA.106.085266
M3 - Article
C2 - 17404185
AN - SCOPUS:34249323778
SN - 0194-911X
VL - 49
SP - 1285
EP - 1290
JO - Hypertension
JF - Hypertension
IS - 6
ER -