Tabulations and expectations regarding the genetics of human hypertension

Abstract

Results from family studies suggest several possible single gene traits may be related to essential hypertension in humans. Results of segregation analysis are reviewed for six possibly related traits (high sodium-lithium countertransport, low urinary kallikrein excretion, high fasting plasma insulin level, a fat pattern index, dense LDL subfractions, and body mass index). Eight genetic loci (on chromosomes 1, 6, 8, 17 and 19) are possibly related to essential hypertension in humans and are also reviewed. Two of them (GRA and AGT) are well-established. Glucocorticoid remediable aldosteronism (GRA) is attributable to a well-defined mutation on chromosome 8q21 and leads to the production of high levels of abnormal adrenal steroid hormones with subsequent aldosteronism, early severe hypertension, and strokes. This form of hypertension is unresponsive to ordinary medications but very responsive to glucocorticoid hormone administration. The angiotensinogen (AGT) locus on chromosome 1q4 has been related to hypertension in sibship linkage studies, association studies, and studies of angiotensinogen levels by genotype in three different populations (Utah, France, Japan). This locus seems to be associated with more severe essential hypertension and also with preeclampsia. Genetic heterogeneity, imprecision in measuring specific phenotypes, and variability in sampling methods in populations studied may all contribute to weaknesses and inconsistencies between reported studies. However, growing evidence for several single gene traits promoting susceptibility to hypertension offers opportunities for identifying genetically profiled subsets of patients in whom specific environmental interventions or specific types of medications will achieve more focused prevention and treatment of hypertension and its complications.