Abstract P235: The Additive Genetic Association of Beta-2 Adrenergic Receptor and Serum-and-Glucocorticoid-Inducible Kinase 1 on Salt-Sensitive Hypertension

Abstract

Salt sensitivity of blood pressure (SSBP) is associated with increased cardiovascular morbidity. A diplotype on the beta 2 adrenergic receptor (β2AR) gene (rs1042713, rs1042714)—associated with increased aldosterone (ALDO)—and a polymorphism in the serum-and-glucocorticoid-inducible kinase 1 (SGK1) gene (rs2758151)—an ALDO target that increases sodium reabsorption—are each associated with SSBP. We hypothesized that SSBP will be increased in homozygotes for both β2AR and SGK1 (Combo) when compared to non-risk homozygotes and homozygotes in either gene alone. The HyperPATH database includes individuals who completed 7 days of both restricted and liberal sodium diets to determine systolic SSBP. We conducted a gene association study in 329 individuals: 42 were homozygotes for Combo; 242 were homozygotes for β2AR or SGK1; and 45 were non-carriers. Multivariate regression analyses (adjusted for age, sex, BMI, race, hypertension) found a significantly higher SSBP in the Combo homozygotes when compared to non-carriers and homozygotes for either β2AR or SGK1(p<0.001, 95% CI: 2.35, 7.56) (Figure 1). Serum ALDO levels were higher in Combo homozygotes than in the other groups (p=0.035, CI: 0.069,1.87). Additionally, analyses of either gene alone with SSBP (β2AR: p=0.056, CI: -0.038, 2.89; SGK1: p=0.003, CI: 0.87, 4.35) was less than what was observed in the Combo. In sum, Combo homozygotes for SGK1 and β2AR substantially increased the level of SSBP compared to that observed in risk allele homozygotes in each gene alone. Thus, hypertensive Combo homozygotes are likely candidates for mineralocorticoid receptor antagonist therapy—gene driven, personalized medicine. Figure 1.