Genetic polymorphisms related to the renin–angiotensin–aldosterone system and response to antihypertensive drugs

Taverne, Kim; Groot, Mark de; Boer, Anthonius de; Klungel, Olaf H.

doi:10.1517/17425250903571670

Cited by 13 publications

(10 citation statements)

References 60 publications

(124 reference statements)

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“…8 Some studies have investigated the effect of the ACE I/D polymorphism on BP response in patients with cardiovascular disease treated with ACE inhibitors (ACEIs). [9][10][11][12][13][14] Several studies have indicated that the D allele had a stronger BP-lowering effect, [15][16][17] while a few studies failed to show the association of I/D polymorphism in lowering the blood pressure. 18,19 The conflicting results made unclear to ability to predict whether the insertion or deletion allele of the I/D polymorphism of the ACE gene influences the response to ACEIs.…”

Section: Introductionmentioning

confidence: 99%

Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene among Malay male hypertensive subjects in response to ACE inhibitors

Heidari

Ramachandran

Ali³

et al. 2014

J Renin Angiotensin Aldosterone Syst

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Introduction: Several studies show that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with hypertension in various populations. The present study sought to determine the association of the I/D gene polymorphism among Malay male essential hypertensive subjects in response to ACE inhibitors (enalapril and lisinopril). Materials and methods: A total of 72 patients with newly diagnosed hypertension and 72 healthy subjects were recruited in this study. Blood pressure was recorded from 0 to 24 weeks of treatment with enalapril or lisinopril. Genotyping of the I/D polymorphism was carried out using a standard PCR method. Results: Statistically significant association of the D allele of the ACE gene was observed between the case and control subjects (p < 0.01). There was a decrease in blood pressure in the patients carrying the DD genotype (SBP=18.5±8.1 mmHg, DBP=15.29±7.1 mmHg) rather than the ID (SBP=4.1±3.3 mmHg, DBP=9.1±3.5 mmHg) and II genotypes (SBP= 3.0±0.2 mmHg, DBP 0.11±6.1 mmHg) of the ACE gene. Conclusion: Patients carrying the DD genotype had higher blood pressure-lowering response when treated with ACE inhibitors enalapril or lisinopril than those carrying ID and II genotypes, suggesting that the D allele may be a possible genetic marker for essential hypertension among Malay male subjects.

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Section: Introductionmentioning

confidence: 99%

Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene among Malay male hypertensive subjects in response to ACE inhibitors

Heidari

Ramachandran

Ali³

et al. 2014

J Renin Angiotensin Aldosterone Syst

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“…Essential hypertension is the leading cause of cardiovascular morbidity and mortality worldwide, affecting about 20% of the adult population and only 23%-41% of hypertensive patients receiving antihypertensive drugs achieve adequate blood pressure control [1,2] . Many drugs are effective in treating hypertension, although individuals can respond differently to the same drug.…”

Section: Introductionmentioning

confidence: 99%

“…Many drugs are effective in treating hypertension, although individuals can respond differently to the same drug. Interindividual variation in the efficacy of medications may be influenced by genetic variations [2][3][4] . Hypertension pharmacogenetics seeks to find genetic predictors of response to drugs that lower blood pressure.…”

Section: Introductionmentioning

confidence: 99%

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Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients

2011

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Aim: To study the relationship between the antihypertensive response of iptakalim and KCNJ11 polymorphisms in Chinese Han hypertensive patients. Methods: One hundred sixty two Chinese Han hypertensive patients were administered iptakalim (5 or 10 mg/d, po) for 8 weeks.Before the treatment and 24 h after completing the treatment blood pressure (BP) was measured. Genotyping was performed using direct sequencing. Results: Four common A190A, E23K, I337V and 3'UTR +62 G/A polymorphisms were found in KCNJ11. The E23K, I337V and 3'UTR +62 G/A polymorphisms were in complete linkage disequilibrium, and I337V was used as a representative. There were no significant differences in age, body mass index, sex, baseline systolic BP (SBP) and diastolic BP (DBP) among the 3 genotypes for the four polymorphisms. Significant association was found between SBP response and the polymorphisms (adjusted regression coefficient: 3.5 [1.2] mmHg; P=0.003 for the A190A polymorphism; adjusted regression coefficient: 3.1 [1.2] mmHg; P=0.012 for the I337V polymorphism). The patients with TT genotype for A190A polymorphism had higher clinical efficacy than those with CC genotype. Conclusion:The results suggest the KCNJ11 polymorphisms are associated with the SBP-lowering response of short-term iptakalim therapy in Chinese Han hypertensive patients.

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“…Hence, blockade with AT 1 R blockers (ARBs) is an important treatment for hypertension and associated cardiovascular and kidney disease (9). However, antihypertensive responses to ARBs vary in different patient populations, suggesting that polymorphisms of the PTC AT 1 R may play a role in differential BP responses to ARBs (1,27,34,37).…”

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Angiotensin type 1 receptor resistance to blockade in the opossum proximal tubule cell due to variations in the binding pocket

Nistala

Andresen

Pulakat

et al. 2013

American Journal of Physiology-Renal Physiology

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Blockade of the angiotensin (ANG) II receptor type 1 (AT(1)R) with angiotensin receptor blockers (ARBs) is widely used in the treatment of hypertension. However, ARBs are variably effective in reducing blood pressure, likely due, in part, to polymorphisms in the ARB binding pocket of the AT(1)R. Therefore, we need a better understanding of variations/polymorphisms that alter binding of ARBs in heterogeneous patient populations. The opossum proximal tubule cell (OKP) line is commonly used in research to evaluate renal sodium handling and therefore blood pressure. Investigating this issue, we found natural sequence variations in the opossum AT(1)R paralleling those observed in the human AT(1)R. Therefore, we posited that these sequence variations may explain ARB resistance. We demonstrate that OKP cells express AT(1)R mRNA, bind (125)I-labeled ANG II, and exhibit ANG II-induced phosphorylation of Jak2. However, Jak2 phosphorylation is not inhibited by five different ARBs commonly used to treat hypertension. Additionally, nonradioactive ANG II competes (125)I-ANG II efficiently, whereas a 10-fold molar excess of olmesartan and the ANG II receptor type 2 blocker PD-123319 is unable to block (125)I-ANG II binding. In contrast, ANG II binding to OKP cells stably expressing rat AT(1A)Rs, which have a conserved AT(1)R-binding pocket with human AT(1)R, is efficiently inhibited by olmesartan. A novel observation was that resistance to ARB binding to opossum AT(1)Rs correlates with variations from the human receptor at positions 108, 163, 192, and 198 within the ARB-binding pocket. These observations highlight the potential utility of evaluating AT(1)R polymorphisms within the ARB-binding pocket in various hypertensive populations.

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Genetic polymorphisms related to the renin–angiotensin–aldosterone system and response to antihypertensive drugs

Abstract: Little evidence is available that explains these pharmacogenetic interactions. In the future, a better understanding of these mechanisms should provide a more solid evidence base for the individualized hypertension treatment based on genetic variation.

Cited by 13 publications

References 60 publications

Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene among Malay male hypertensive subjects in response to ACE inhibitors

Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene among Malay male hypertensive subjects in response to ACE inhibitors

Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients

Angiotensin type 1 receptor resistance to blockade in the opossum proximal tubule cell due to variations in the binding pocket

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