P. Corvol et al., Seven lessons from two candidate genes in human essential hypertension - Angiotensinogen and epithelial sodium channel, HYPERTENSIO, 33(6), 1999, pp. 1324-1331
Citations number
67
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
The candidate gene approach to understanding the genetics of human essentia
l hypertension is discussed by analyzing the contribution of 2 genes, angio
tensinogen (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 pressu
re variance. Mutations of the beta- and gamma-ENaC subunits are responsible
for Liddle's syndrome, but the implication of the 3 ENaC subunits in essen
tial hypertension is still questionable. Several lessons can be learned fro
m these studies and applied to other candidate genes in essential hypertens
ion: (1) Many Linkage or association studies have a limited statistical pow
er; (2) The genetic findings may vary greatly according to the populations
studied; (3) There is a need for better phenotyping of the hypertensive pop
ulation; (4) The causal relationship between molecular variants and hyperte
nsion 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 attributabl
e 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 d
rug treatment according to patients' genotypes.