Abstract 18068: Basis for a Major Genetic Alteration in Essential Hypertension: Inherited Defect in RBC-K Function and Oxygen Transport

Abstract

For decades, the pathogenesis and management of hypertension have been focused on dietary salt consumption, low potassium (K) intake, or hormonal factors triggering elevation of BP. In this context, our description of an inherited defect in RBC-K transport serially recorded in hypertensive subjects and in 52% of their normotensive adolescents offspring implies a genetic defect from erythropoietic cells and a biochemistry abnormalities in the circulating RBC as K-dependent pyruvate kinase activity for ATP synthesis, or allosteric K-O2 binding by hemoglobin, recently described by our Laboratory. Methods: A pedigree analysis was performed in randomized hypertensive patients (HT, aged ≥30-years) with essential hypertension (BP>140/90 mmHg), confirmed in the last 3-years, and having low RBC K content (<92 mmol/l of cell). Normotensive (NT) group were healthy subjects matched for sex-age-race and having normal BP and higher RBC-K. Family data includes sex-age-race of parents, siblings, spouses, children and presence of hypertension, diabetes (D), coronary heart diseases (CHD) and Stroke. For each family the number of deceased, age and cause of death were accurately obtained. Results: Fifty two hypertensive subjects disclosed family data (104 parents, 219 siblings, 24 spouses and 64 children= 411 cases) with large number of HT and CV disease: a) Parents: 63 hypertensive and 15 diabetic HT (75% incidence) with 3 AMI, 3 Stroke, 1 CRF and 21 CV deaths at age 58±7; b) Siblings: 142 out of 219 were HT (64.8 %; range 33-90%), 7 of them Stroke, 4 DM, CAD 15, 25 CV deaths at age 58±10 year; c) spouse 8 HT 33 %, children: <30 years (9, 14% HT), ≥30 years, 15 HT, 23%), the remaining being NT. From 104 HT parents were born 142 HT (17 CV deaths, 125 alive, aged 52±6). In contrast, from 24 NT subjects there were: 48 parents, 153 siblings, 16 spouses and 48 children (total 265): a) Parents: 12 HT (25%), 2 AMI, 5 CAD, 3 DM, 13 no CV deaths at age 73±7 years; Siblings: 14 HT (9.2%) 7 DM, CV, no deaths, all alive aged 52±7; c) spouses HT 29%, children 7 HT, 14.5%. From 48 NT parents were born only 14 HT subjects. In Conclusion: This study strongly suggests the presence of a major hereditary defect in essential hypertension, involving defective RBC-K transport and function.