Plasma Endothelin of Sibpairs: Variability, Inheritance, and Linkage to Obesity in Essential Hypertension
A polymorphism of the endothelin (ET)-1 gene has been associated with blood pressure (BP) of obese individuals in large population studies. We explored the variability of plasma ET in essential hypertensive sibpairs (n=14 pairs, 13 with two sibs, 1 with three sibs) in relationship to their body mass index (BMI). ET levels were measured on ad libitum Na intake (AL), after a 24 hr Na load (300 mEq iv +160 mEq po, HI) and after 24 hr of Na deprivation (10 mEq po + furosemide 120 mg, LO). BP was 147±3/90±2 mmHg and BMI 35.1±1.4, with 75% of patients exceeding 30 Kg/m2. ET was 4.4±0.3, 4.1±0.2, and 4.3±0.3 fmol/ml for AL, HI and LO, respectively, all higher than 20 controls (3.3±0.3, ps <0.04). One way ANOVA disclosed that ET variability within pairs was significantly less than that between pairs. This was true for each diet and for all diets combined, with maximal statistical significance after the fixed Na load (F=18.9, p <0.0001). The sibpair variance of plasma ET(AL) exhibited a negative correlation with BMI (r=-0.51, p<0.01) but did not correlate with the sibpair variance for BMI. In an ANCOVA with family ID as main effect and BMI as the regressor covariate, individual ET(AL) was explained by family ID, independent of BMI (Model: R2=0.79, F=3.2, p<0.02; Family ID: p<0.03; BMI: ns). Our data suggest that inheritance plays a major role in determining plasma ET of essential hypertensive patients, while salt-balance has a small additional effect. The concordance of ET levels in sibpairs increases with the magnitude of obesity, but this effect of BMI is explained by family ID in the covariate analysis. These results suggest that there is a link between the inheritance of obesity and ET in hypertension, consistent with observations in population studies.