New results have been obtained on the possible role of the angiotensinogen gene, and other candidate genes, such as the angiotensin II receptor Type I gene and the Sa gene, in human hypertension.
The type 1 angiotensin II receptor (AT1) genes are obvious hypertension candidate genes, whereas the SA gene has recently been shown to cosegregate with hypertension in the rat.
A transversion of adenine to cytosine at nucleotide position 1166 in the gene coding for the angiotensin-II type 1 receptor has been associated with hypertension in the non-diabetic population.
Our objective in this investigation was to determine if a virally mediated gene-transfer approach using angiotensin type 1 receptor antisense (AT1R-AS) could be used to control hypertension on a long-term basis in the SH rat model of human essential hypertension.
Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals.
These results suggest that the AGT and AT1 receptor genes are not major genetic determinants of hypertension associated with NIDDM in this population, although we can not exclude the possibility that these loci make a minor contribution in a polygenic context.
Regulatory actions of angiotensin II (AngII), which is involved in the pathophysiology of hypertension and also participates in cell proliferation and cell differentiation, are mainly mediated by AngII type 1 (AT1) receptor.
We conclude that there is no significant association between the hypertension associated AT1R gene polymorphism and diabetic nephropathy in patients with IDDM in the UK.
We detected no association of the AT1 receptor polymorphism with hypertension, but a trend towards a decreased prevalence of the 1166C allele among hypertensive patients with a late age at diagnosis (> or = 50 years) was observed.
These results suggest that increased activation of central AT-1 receptors, perhaps those located at sites involved in AVP release from the posterior pituitary gland, plays a role in the hypertension in RA+ mice.
These stratifications yielded suggestive evidence for linkage of hypertension to the genetic area containing the AT1 gene, with a maximal multipoint logarithm of the odds (LOD) score of 2.9.
It has recently been reported that the risk of developing nephropathy in patients with insulin dependent (type 1) diabetes mellitus is strongly associated with synergism between poor glycaemic control and carriage of the hypertension associated angiotensin II (type 1) receptor C1166 allele.
From the present data it is unlikely that any one of the nine newly characterized SNPs in the promoter region of AT1 gene is associated with arterial hypertension.
The finding of polymorphic sites in the functional promoter of the human AT1 locus will be beneficial to the study of the role of the AT1 receptor gene in hypertension and other cardiovascular diseases.
In this review, we discuss the role of renin-angiotensin system (RAS) in hypertension; the current gene delivery/gene transfer systems and the RAS as a target for gene therapy to treat hypertension; the successful use of retroviral vectors to deliver antisense to the AT1 receptor (AT1-AS) to prevent the development of hypertension and cardiovascular pathophysiology; the potential use of the viral vectors for the reversal of hypertension; and the future of antisense gene therapy and potential advantages and limitations of this regimen in the treatment and/or control of hypertension.
Three of the loci are in the renin-angiotensin-system, angiotensinogen, ACE, and angiotensin II type 1 receptor, and they have been associated with hypertension in at least 1 previous study.
Because hypertension and renal hemodynamic function are also related to the risk of diabetic nephropathy and because hyperglycemia can activate the renin angiotensin system, we sought to determine if there is an association between the AGT1R polymorphism, baseline renal and peripheral hemodynamic function, and pressor response to high glucose in subjects with early uncomplicated type 1 diabetes.