HYPOTHESIS: GLUCAGON RECEPTOR GLYCINE TO SERINE MISSENSE MUTATION CONTRIBUTES TO ONE IN 20 CASES OF ESSENTIAL HYPERTENSION

SUMMARY 1. A missense mutation leading to reduced ligand affinity in the glucagon receptor (GCG-R) has been found recently to be five-fold more common in essential hypertensives than normotensives. The present paper provides additional information on patients that harbour this variant and proposes a possible mechanism by which this may lead to hypertension. 2. The seven hypertensives with the mutation were all female, had a later age of onset of the disease and a slightly higher body mass index. 3. Glucagon is involved in the regulation of fluid and electrolyte excretion. Mutant GCG-R results in reduced ligand affinity and cAMP response which, in the kidney, would reduce the normal natriuretic effect of glucagon. This could lead to enhanced fluid reabsorption, expansion of extracellular fluid volume and hypertension via long-term autoregulation of blood pressure.