Impact of Two Polymorphisms of the Angiotensin Ii Type 1 Receptor Gene on Renal Function

Spiering, W.; Chaves, F.J.; Fuss-Lejeune, M. J.M.J.; Daemen, M. J. A. P.; Redón, Josep; Leeuw, Peter W. de

doi:10.1097/00004872-200006001-00392

Cited by 3 publications

(4 citation statements)

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“…In a human association study reported in the same article, carriers of this polymorphism who have heart failure seem to have lower mortality and greater freedom from cardiac transplantation. Similar evaluation has been performed with the human AT1aR polymorphism A1166C, which demonstrates increased vasoconstrictor activity in patients with hypertension (Amant et al, 1997;Spiering et al, 2000). Only one small pilot study has demonstrated a beneficial interaction between the ARB candesartan and this polymorphism (de Denus et al, 2008).…”

Section: Polymorphic Variation In Adrenergic and Angiotensin Receptorsmentioning

confidence: 89%

Functional Selectivity in Adrenergic and Angiotensin Signaling Systems

Patel

Noor²,

Rockman

2010

Mol Pharmacol

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␤-Adrenergic and angiotensin II type 1A receptors are therapeutic targets for the treatment of a number of common human diseases. Pharmacological agents designed as antagonists for these receptors have positively affected the morbidity and mortality of patients with hypertension, heart failure, and renal disease. Antagonism of these receptors, however, may only partially explain the therapeutic benefits of ␤-blockers and angiotensin receptor blockers given the emerging concept of functional selectivity or biased agonism. This new pharmacological paradigm suggests that multiple signaling pathways can be differentially modified by a single ligand-receptor interaction. This review examines the functional selectivity of ␤-adrenergic and angiotensin II type 1A receptors with respect to their ability to signal via both G protein-dependent and G protein-independent mechanisms, with a focus on the multifunctional protein ␤-arrestin. Also highlighted are the concept of "biased signaling" through ␤-arrestin mediated pathways, the affect of ligand/receptor modification on such biased agonism, and the implications of functional selectivity for the development of the next generation of ␤-blockers and angiotensin receptor blockers.

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Section: Polymorphic Variation In Adrenergic and Angiotensin Receptorsmentioning

confidence: 89%

Functional Selectivity in Adrenergic and Angiotensin Signaling Systems

Patel

Noor²,

Rockman

2010

Mol Pharmacol

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“…In addition, we found that the sympathetic parameters of HRV were higher in AT 1 R 1166C allele carriers in a standing position, in which both the sympathetic system and RAS could be activated. Although a molecular functional role for this point mutation in the 3Ј untranslated region of the AT 1 R gene has not been demonstrated so far, it can be hypothesized that the AT 1 R A1166C polymorphism may be in linkage disequilibrium with other functional genetic variants affecting the expression or properties of AT 1 R. Some reports have indicated that the AT 1 R 1166C allele is associated with increased humoral and hemodynamic sensitivity to angiotensin II (34,35), and a significant relationship between this polymorphism and hypertension, CVD, myocardial infarction, vascular stiffness, and left ventricular hypertrophy has also been reported (8,9). Through AT 1 R, angiotensin II enhances the sympathetic system in both central and peripheral sites (1-4), and AT 1 R antagonists have been used clinically to decrease catecholamine release in chronic heart failure patients with an overactivated RAS (7).…”

Section: Discussionmentioning

confidence: 99%

Genetic Variation in the Renin-Angiotensin System and Autonomic Nervous System Function in Young Healthy Japanese Subjects

Nishikino

Matsunaga²,

Yasuda

et al. 2006

The Journal of Clinical Endocrinology & Metabolism

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“…7 This suggests that the effect of AII may be enhanced in carriers of the C allele of the AT1R A1166C polymorphism. 4,[25][26][27] It is noted that AII infusion decreases plasma adiponectin levels through its type 1 receptor in rats, 10 and treatment with an AII type 1 receptor antagonist increases plasma adiponectin levels in hypertensive patients. 12 These results suggest that a difference in activation of the local RAS may be directly involved in the variation between genotypes with regard to plasma adiponectin concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…A common polymorphism in the AT1R (A1166C) has been linked to enhanced physiological responses to AII. 4 In addition, this polymorphism in the human AT1R has been associated with phenotypic effects including insulin sensitivity and metabolic syndrome traits as well as high blood pressure. 5,6 Although this polymorphism is located in the 3¢-untranslated region of the human AT1R, recent evidence shows that the polymorphism can lead to increased AT1R densities through inhibition of the ability of miR-155 to attenuate translation of AT1R mRNA.…”

Section: Introductionmentioning

confidence: 99%

C allele of angiotensin II type 1 receptor gene A1166C polymorphism affects plasma adiponectin concentrations in healthy young Japanese women

et al. 2009

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Angiotensin II and its type 1 receptor (AT1R) are both expressed in the adipose tissue and involved in the genesis of atherosclerosis as well as hypertension. However, the influence of the AT1R gene A1166C polymorphism on atherosclerosis risk factors and on the development of early atherosclerosis is not clear. We evaluated 416 healthy young women to investigate the effects of this genotype on atherosclerosis risk factors and on carotid intima-media thickness as a validated marker of early atherosclerosis. After adjusting for confounding factors including body mass index, homeostasis model assessment of insulin resistance and plasma high-density lipoprotein (HDL)-cholesterol levels, plasma adiponectin concentrations were significantly lower in carriers of the C allele compared with non-carriers. Moreover, multiple logistic regression analysis showed that the C allele was the strongest and most independent determinant of lower plasma adiponectin concentrations. It is noted that the participants with the lowest quartile of plasma adiponectin concentrations had thicker levels of carotid intima-media thickness, lower plasma HDL-cholesterol and lipoprotein lipase levels, as well as higher trunk fat mass compared with the highest quartile. In addition, a weak but significant positive correlation was observed between percentages of fat in the diet and plasma adiponectin concentrations in non-carriers of the C allele. In conclusion, AT1R A1166C was associated with plasma adiponectin concentrations and influenced the correlations between dietary fat intake and plasma concentrations of adiponectin. These findings may help to identify vulnerable populations that are susceptible to the development of atherosclerosis and require early dietary recommendations for young women.

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Impact of Two Polymorphisms of the Angiotensin Ii Type 1 Receptor Gene on Renal Function

Cited by 3 publications

References 0 publications

Functional Selectivity in Adrenergic and Angiotensin Signaling Systems

Functional Selectivity in Adrenergic and Angiotensin Signaling Systems

Genetic Variation in the Renin-Angiotensin System and Autonomic Nervous System Function in Young Healthy Japanese Subjects

C allele of angiotensin II type 1 receptor gene A1166C polymorphism affects plasma adiponectin concentrations in healthy young Japanese women

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