We have previously described a subset of subjects with essential hypertension who fail to appropriately modulate renal vascular and adrenal reactivity with changes in dietary sodium and in response to infused angiotensin II (Ang II).
A recent cross-sectional study of HTs in Salt Lake City and Paris has reported a significant association of a T704-->C (Met235-->Thr) variant in exon 2 of the angiotensinogen gene (AGT) with essential hypertension (HT).
In a series of Caucasian women with pregnancy-induced hypertension, we have observed a significant association of preeclampsia with a molecular variant of angiotensinogen, T235, found previously to be associated with essential hypertension.
Many persons with essential hypertension carry a common "susceptibility gene" at the angiotensinogen locus (chromosome 1q4) identified using linkage studies in siblings, association studies, and in studies of preeclampsia and hypertension in pregnant women.
These results suggest that abnormalities in the angiotensinogen gene resulting in increased circulating levels of angiotensinogen could potentially contribute in part to the pathogenesis of essential hypertension.
The observation of this association in a distinct, ethnically homogeneous population further substantiates an involvement of angiotensinogen in the pathogenesis of essential hypertension and has physiological, epidemiological, and evolutionary implications.
We found significant linkage (t = 5.00, P < 0.001) and association (chi-square = 53.3, P < 0.001) of the angiotensinogen-gene locus to essential hypertension in the 63 multiplex families.
In the present brief survey on new developments in the drug treatment of essential hypertension, the following issues are summarized: the treatment of hypertension in diabetics, patients with left ventricular hypertrophy, and the elderly; new antihypertensive drugs, including a hybrid (multifactorial) antihypertensive drug with both calcium and alpha 1-adrenoceptor antagonistic activity, as well as angiotensin II-receptor antagonists; and finally, gene therapy in hypertension.
These results suggested that this molecular variant of the angiotensinogen gene may be a preserved inherited predisposition for essential hypertension in various ethnic groups, including Caucasians and Japanese.
In a separate study, the T235 homozygote of the angiotensinogen gene was associated with the non-modulating intermediate phenotype of essential hypertension.
These results suggest that the contribution of variation in the angiotensinogen gene to the occurrence of essential hypertension is less than initially suspected, or may not be constant across populations.
These data provide evidence in favour of an association between hypertension and a genetic variant of AGT in human EHT, and a marked ethnic difference in the AGT gene.
These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity.
Angiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues.
To date, mutations in three genes have been implicated in the pathogenesis of human hypertension: mutations resulting in ectopic expression of aldosterone synthase enzymatic activity cause a mendelian form of hypertension known as glucocorticoid-remediable aldosteronism; mutations in the beta subunit of the amiloride-sensitive epithelial sodium channel cause constitutive activation of this channel and the mendelian form of hypertension known as Liddle syndrome; finally, common variants at the angiotensinogen locus have been implicated in the pathogenesis of essential hypertension in Caucasian subjects, although the nature of the functional variants and their mechanism of action remain uncertain.
Variants of the human angiotensinogen gene have been linked in some studies to increased circulating angiotensinogen levels and essential hypertension.
The TT genotype of a polymorphism encoding threonine instead of methionine (M235T) has been associated not only with increased plasma angiotensinogen concentration but also with essential hypertension.
There are now two studies in populations of white European origin and one in African Caribbeans providing support for a role of the angiotensinogen gene locus in human essential hypertension.
The allele 235T (a threonine in place of a methionine at position 235) of angiotensinogen has been found to be associated with a predisposition to essential hypertension.