The causes of essential hypertension

Abstract

1. Confusion between the criteria for defining and diagnosing hypertension may have misled the search for the causes of hypertension. 2. The systematic approach of molecular genetics appears to offer the best chance of explaining hypertension, but the attractions are partly offset by the large numbers required, and unproven record of the genetic techniques in finding functional mutations in complex human disorders. 3. Part of the evidence for the polygenic nature of essential hypertension derives from the variable response to a large number of different anti-hypertensive agents. Systematic investigation of this variability may provide a basis for dividing patients into genetically more homogeneous sub-groups, within which smaller numbers will be required to detect the genes responsible for the susceptibility to hypertension. 4. The proportion of hypertensive patients with affected siblings has been studied in 6000 patients from Addenbrookes Hospital and local general practices. A recurrence risk for hypertension of approximately 3.5 was found. 5. Approximately two-thirds of patients have no known affected siblings. The next largest group, about one third, is patients whose siblings are all hypertensive. In a small group, < 10% of all patients, half the siblings are hypertensive. 6. We conclude from these surprising findings that hypertension is not a continuous, multifactorial part of the normal blood pressure distribution. They suggest that several more single-gene disorders causing hypertension will be found. The sibships where all members are hypertensive are inconsistent with the segregation of Mendelian genetics and suggest the selection of some genes linked to hypertension at the time of gamete maturation.