Evidence for single gene contributions to hypertension and lipid disturbances: definition, genetics, and clinical significance

Roger R. Williams, Steven Hunt, Paul N. Hopkins, Lily L. Wu, Jean Marc Lalouel

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Several large family studies are reviewed to identify results suggesting single gene traits contributing to the occurrence of hypertension in humans. Segregation analysis in families has suggested major gene effects for several highly heritable traits associated with hypertension. These include recessively segregating high sodium‐lithium countertransport (major gene H2= 34%), additively segregating low urinary kallikrein excretion (major gene H2= 51%), and recessively segregating hyperinsulinemia (major gene H2= 33%). In some families, hypertension and metabolic abnormalities (dyslipidemia, hyperinsulinemia, and obesity) seem to be related to several candidate genes studied but not conclusively proven (LPL deficiency mutations, dense LDL subfractions, or NIDDM with hyperinsulinemia). More recently, DNA markers have identified genes promoting hypertension. Glucocorticoid‐remediable aldosteronism (GRA) promotes a rare but unusual form of hypertension that is unresponsive to ordinary medications but very responsive to glucocorticoid medications. GRA has been found in hypertensive persons with a specific mutation of the 11 beta‐hydroxylase gene on chromosome 8q21. Many persons with essential hypertension carry a common “susceptibility gene” at the angiotensinogen locus (chromosome lq4) identified using linkage studies in siblings, association studies, and in studies of preeclampsia and hypertension in pregnant women. These first two well‐established genetic loci promoting human hypertension represent two ends of a broad spectrum. The rare “determinant” gene for GRA by itself seems to produce severe hypertension and early strokes. The angiotensinogen (AGT) “susceptibility” gene is very common (30% of Utah Caucasians) and seems to predispose to hypertension but probably requires other genetic and environmental influences to be fully expressed. An understanding of other genetic and environmental factors that interact with genetic traits like angiotensinogen and kallikrein will probably identify patients in whom specific environmental interventions (such as sodium restriction or potassium supplementation) or specific types of medications will facilitate targeted prevention and treatment of hypertension and its complications.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalClinical Genetics
Issue number1
Publication statusPublished - 1994
Externally publishedYes



  • blood pressure
  • cholesterol
  • epidemiology
  • genetics
  • insulin
  • obesity
  • potassium
  • sodium
  • triglycerides

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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