(Hypertension. 1999;33:1324-1331.)
© 1999 American Heart Association, Inc.
Theodore Cooper Memorial Lecture |
Seven Lessons From Two Candidate Genes in Human Essential Hypertension
Angiotensinogen and Epithelial Sodium Channel
From INSERM U36 - Collège de France, Paris.
Correspondence to Dr P. Corvol, INSERM U36, Collège de France, 3, rue d'Ulm - 75005 Paris, France. E-mail corvol{at}infobiogen.fr
Abstract
Abstract—The candidate gene
approach to understanding the genetics of human essential hypertension
is discussed by analyzing the contribution of 2 genes,
angiotensinogen (AGT) and epithelial amiloride-sensitive
sodium channel (ENaC). From a large series of studies conducted in
humans and animals, it appears that the AGT gene plays a significant
but modest role in human blood pressure variance. Mutations of the ß-
and 
-ENaC subunits are responsible for Liddle's syndrome, but the
implication of the 3 ENaC subunits in essential hypertension is still
questionable. Several lessons can be learned from these studies and
applied to other candidate genes in essential hypertension: (1)
Many linkage or association studies have a limited statistical power;
(2) The genetic findings may vary greatly according to the populations
studied; (3) There is a need for better phenotyping of the hypertensive
population; (4) The causal relationship between molecular variants and
hypertension is and will be difficult to establish firmly; (5) The
contribution of genetic studied in rodents to the molecular genetics of
human hypertension must be re-examined; (6) Most molecular
variants lead to a low attributable risk in the population or a low
individual effect at the individual level; and (7) It is too early to
propose dietary recommendations and specific drug treatment according
to patients' genotypes.
Key Words: angiotensinogen • sodium channel • genetics • blood pressure • hypertension, essential
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