Abstract 258: Endothelium-Dependent Vasodilation in Conduit and Resistance Vessels in Relation to the Endothelial Nitric Oxide Synthase Gene
Background: The role of nitric oxide in vasodilation, and in cardiovascular disease in general, has been of intense interest recent years. Prior community-based studies relating single nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (NOS3) gene to endothelium-dependent vasodilation have provided diverging results, and they have not assessed both conduit or resistance arteries.
Methods: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, 959 participants aged 70 were evaluated by brachial artery ultrasound to assess flow-mediated vasodilation (FMD; reflecting conduit arteries), and invasive forearm technique with intra-brachial infusion of acetylcholine (EDV; reflecting resistance arteries). The 23 SNPs analyzed by minisequencing captured >90% of the common genetic variation in the NOS3 gene, using the HapMap population of European ancestry (CEU) as reference. Haplotypes were estimated using the PHASE software.
Results: One SNP (rs1799983, also known as Glu298Asp) was related to FMD (nominal p=0.0018), but not to EDV (nominal p=0.76) in multivariable analyses (adjusting for sex, systolic blood pressure, diastolic blood pressure, pulse rate, anti-hypertensive treatment, total cholesterol, high-density cholesterol, lipid-lowering medication, fasting glucose, anti-diabetic medication, body mass index, current smoking, and prior diagnosis of cardiovascular disease). Homozygotes of the minor allele (TT) demonstrated a higher FMD than carriers of the common allele. The same pattern was seen in men (P=0.0056) and women (P=0.025), although the effect was more pronounced in men. The association between rs1799983 and FMD remained significant after adjusting for multiple testing (empirical P=0.029, obtained using bootstrap re-sampling). None of the haplotypes were related to either FMD or EDV.
Conclusions: The Glu298Asp SNP in the NOS3 gene was related to endothelium-dependent vasodilation in conduit arteries, but not in resistance arteries. This SNP has previously been related to coronary heart disease, but there is a need for further validation of our findings with regard to endothelial function.