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).
Hypertensive patients carrying the control genotype of rs2074192 (CC, OR = 2.37, 95% CI: 1.28-4.39) were associated with CAS ≥50%, while those carrying a high-EH-risk genotype of rs4240157 (OR = 2.62, 95% CI: 1.24-5.54), rs4646155 (OR = 2.44, 95% CI: 1.16-5.10), or rs4830542 (CC+CT, OR = 2.20, 95% CI: 1.03-4.69) were associated with atrial fibrillation (AF), larger left atrial diameter, and higher levels of renin-angiotensin-aldosterone system (RAAS) activation (renin and angiotensin I/II).
Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB).
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.
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.
Although several arguments from association studies suggest a role of the AGT gene in essential hypertension, this large family study did not replicate the initial linkage reported in smaller studies.
In addition, the T235M polymorphism in the AGT product is associated with an increased risk of essential hypertension in multiple populations, making AGT a good example of a quantitative-trait locus underlying susceptibility to a common disease.
We attempted to evaluate the risk of -217G>A, -152G>A, -20A>C, -6G>A, T174M, M235T and 15241A>G polymorphisms at AGT locus along with the analyses of haplotype and epistatic interactions in causing susceptibility to EHT.
Since AGT is an acute phase protein, we propose that increased expression of -217A allele of the AGT gene by glucocorticoids and C/EBP family of transcription factors may be involved in essential hypertension.
Comparative Efficacy of Angiotensin II Antagonists in Essential Hypertension: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.
We determined the association of angiotensinogen (M235T) gene polymorphism with essential hypertension and the relationship between polymorphism in the angiotensinogen (M235T) gene and blood pressure response to ACE inhibitor (Enalapril) in patients with essential hypertension from northern Indian subjects.
Thus, our findings suggest that in white families with type 2 diabetes, there is no linkage between the degree of albumin excretion and ACE and AGN polymorphisms, whereas the latter is related to arterial hypertension, as previously found in patients without diabetes but with essential hypertension.
We performed a meta-analysis with the aim of assessing the association of the angiotensin II type 1 (AT(1)) receptor gene A1166C polymorphism with essential hypertension in Chinese case-control studies.
Angiotensin II type 1 genotyping and relative telomere length were investigated by PCR in 40 patients of essential hypertension and 15 healthy controls.
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.
RAAS-blocking agents like angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, have long been key components in the treatment of essential hypertension, heart failure, diabetic nephropathy, and chronic kidney disease, showing benefits well beyond blood pressure reduction.
The issues confronting the genetic analysis of EH are discussed by drawing from our ongoing work along the hypothesis that molecular variants of the angiotensinogen gene may constitute inherited predispositions to the condition.
The hypothesis that genetic variation at the angiotensinogen locus impacts on individual susceptibility to develop essential hypertension has motivated a substantial body of research by us and many others.
Our results suggest that the positive association between angiotensinogen gene polymorphisms and haplotypes with essential hypertension is not simply explained by an increase in plasma angiotensinogen concentration.