Common genetic variation in KCNH2 is associated with QT interval duration: the Framingham Heart Study.

Background: QT prolongation is associated with increased risk of sudden cardiac death in the general population and in people exposed to QT-prolonging drugs. Mutations in the KCNH2 gene encoding the HERG potassium channel cause 30% of long-QT syndrome, and binding to this channel leads to drug-induced QT prolongation. We tested common KCNH2 variants for association with continuous QT interval duration.

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

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.

Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample.

Aldosterone:renin ratio (ARR) is used to screen for hyperaldosteronism. Data regarding correlates of ambulatory ARR in the community and its relation to hypertension incidence are limited. We defined clinical correlates of ARR, determined its heritability, tested for association and linkage, and related ARR to blood pressure (BP) progression in nonhypertensive individuals among 3326 individuals from the Framingham Heart Study (53% women; mean age: 59 years).

Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk.

Objective: We undertook a linkage disequilibrium (LD)-based genetic approach to investigate the hypothesis that common sequence variants in 5 thrombosis genes influence plasma hemostatic protein levels or risk of cardiovascular disease (CVD).

Methods And Results: In a reference panel, we characterized LD structure at the fibrinogen gene cluster (fibrinogen-beta[FGB], FGA, and FGG), factor VII (F7), and tissue plasminogen activator (PLAT) loci. Forty-one tag single nucleotide polymorphisms (SNPs) were genotyped in 1811 unrelated Framingham Heart Study participants.

Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum C-reactive protein level.

Background: Serum C-reactive protein (CRP) level is a heritable complex trait that predicts incident cardiovascular disease. We investigated the clinical and genetic sources of interindividual variability in serum CRP.

Methods And Results: We studied serum CRP in 3301 Framingham Heart Study (FHS) participants (mean age 61 years, 53% women).