Genetic polymorphisms of the angiotensin II type 1 receptor gene and diastolic heart failure

Wu, Cho Kai; Tsai, Chia Ti; Chang, Yi‐Cheng; Luo, Jing; Wang, Yi Chih; Hwang, Juey Jen; Lin, Jiunn Lee; Tseng, Chuen Den; Chiang, Fu-Tien

doi:10.1097/hjh.0b013e32831fda3a

Cited by 61 publications

(48 citation statements)

References 28 publications

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“…[25][26][27] Our recent studies found that patients with the ACE I/D gene D allele and AT1R gene A1166C C allele in RAS genes were more likely to develop DHF. 28,29 In this study, we demonstrated that the ACE I/D gene D allele and AT1R gene A1166C C allele were associated not only with the development of DHF but also with the long-term prognosis. Furthermore, the genetic association of the ACE I/D polymorphism with mortality was prominent in those who did not take ACE inhibitors, but was not significant in the patients who took ACE inhibitors.…”

Section: Survival Free Of Death From Cardiovascular Eventsmentioning

confidence: 52%

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure

Jl²,

Tsai

et al. 2009

Pharmacogenomics J

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The objective of this study was to evaluate the effects of angiotensin-converting enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure (DHF). A total of 285 subjects with DHF confirmed by echocardiography were recruited in the period between 1995 and 2003. Baseline characteristics (age, sex, prior history, medication, and echocardiographic findings) and genetic polymorphisms (ACE gene insertion/ deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of the angiotensin II type I receptor (AT1R)) were collected and matched (by propensity score) in those who received and those who did not receive ACE inhibitors. The patients were followed up to 10 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival trend. The 85 patients who received ACE inhibitors and the other 85 patients who did not were found to have comparable baseline characteristics and polymorphism distribution. Prescription of ACE inhibitors was associated with a significant decrease in overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24-0.83; P ¼ 0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53; 95% CI, 0.32-0.90; P ¼ 0.02). In addition, ACE I/D gene D allele was associated with higher overall mortality as compared with the I allele (HR, 2.04; P ¼ 0.003). This effect was diminished in those who received ACE inhibitors. The use of ACE inhibitor was associated with a significant decrease in long-term mortality and cardiovascular events in the patients with DHF. Genetic variants in the renin-angiotensin system genes were also associated, but their effects could be modified by the use of ACE inhibitors.

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Section: Survival Free Of Death From Cardiovascular Eventsmentioning

confidence: 52%

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure

Jl²,

Tsai

et al. 2009

Pharmacogenomics J

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“…However, the other three candidate genes, namely, AGTR1, PRRC2A, and CALCA, were not found to be associated with hypertension in the Chinese Han population after adjustment by age and gender; these findings disagree with those of previous studies. Angiotensin II receptor type-1 (AGTR1) is a G-protein coupled receptor for angiotensin II, especially in the heart and kidney, and has been studied in many health conditions, including heart failure and stroke (Henskens et al, 2007;Wu et al, 2009). AGTR1 polymorphisms are associated with the susceptibility to hypertension and prehypertension in the American population (Mottl et al, 2008;Fung et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Genetic variations in MOV10 and CACNB2 are associated with hypertension in a Chinese Han population

Hong¹,

Chen²,

Liu³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Human hypertension is a complex, multifactorial disease. Multiple variants associated with hypertension have been identified in the large numbers of genome-wide association studies, meta-analysis, and case-control studies. The present study investigated the association between the single nucleotide polymorphisms (SNPs) of five candidate genes and the susceptibility and prognosis of hypertension in a Chinese Han population. A hospital-based case-control study in a Chinese Han population was carried out, including 500 hypertension patients and 506 healthy controls. The five SNP markers were detected using the Sequenom MassArray ® iPLEX System. The association of genotypes with susceptibility to hypertension was analyzed using odds Association of genetic polymorphisms and hypertension ratio, with 95% confidence interval and logistic regression. All five variants conformed to Hardy-Weinberg proportions in the controls. No significant differences were noted in the genotype distributions for AGTR1, PRRC2A, and CALCA polymorphisms in patients with hypertension (N = 500) and healthy controls (N = 506). SNP rs2932538, a variant in MOV10, was found to be significantly associated with an increased risk of hypertension. However, SNP rs4373814, a variant in CACNB2, showed a relevant association with a decreased risk of hypertension. In conclusion, the results of our case-control study confirmed the significant association of the SNP rs2932538 in MOV10 and SNP rs4373814 in CACNB2 with an increased risk of hypertension in a Chinese Han population, suggesting that the SNP rs2932538 may be a poor prognostic indicator for hypertension, while SNP rs4373814 may be a good prognostic indicator for hypertension in the same region. However, our findings need to be replicated in larger epidemiological and functional studies.

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“…It has been reported that AGTR1 polymorphisms are related to susceptibility to EH. [7][8][9]22 AGTR1 played an important role in vasoconstriction, aldosterone and vasopressin release and salt and water retention. RAAS was implicated as one major effector of EH.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms within angiotensin II receptor type 1 gene associated with essential hypertension in Chinese Hani and Yi minorities

Yang

Bai

et al. 2015

J Renin Angiotensin Aldosterone Syst

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Introduction: Angiotensin II receptor type 1 mediates the major cardiovascular effects of angiotensin II to regulate blood pressure. Polymorphisms of angiotensin II receptor type 1 are associated with essential hypertension, but the results are inconsistent and conflicting. The aim of the present study is to assess the association between angiotensin II receptor type 1 polymorphisms and essential hypertension risk in Chinese Hani and Yi minorities. Methods: This study recruited 692 unrelated Chinese Hani subjects (case vs. control = 346:346) and 615 unrelated Chinese Yi subjects (case vs. control = 303:312). Twelve selected single nucleotide polymorphisms in the angiotensin II receptor type 1 gene were genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. Results: Statistical analysis indicated that the GC+CC genotype of rs387967 was significantly associated with the decreased susceptibility to essential hypertension compared with GG in a Yi population (odds ratio = 0.58, 95% confidence intervals 0.41–0.83, P = 0.003). Allele C was a protective allele for essential hypertension (odds ratio = 0.78, 95% confidence intervals 0.61–0.99, P = 0.040). This association was confirmed respectively by comparing systolic blood pressure and diastolic blood pressure between different genotypes and between different alleles, which indicated that the genotype (GC+CC) had a tendency of lower systolic blood pressure and diastolic blood pressure than GG (PSBP = 3.716 × 10–4, PDBP = 1.187 × 10–3); Carriers with C had lower systolic blood pressure and diastolic blood pressure (PSBP = 7.301 × 10–3, PDBP = 9.142 × 10–4). Another single nucleotide polymorphism (rs2638360) was analysed in a Hani minority, then replicated in a Yi minority. The C allele showed a consistent risk trend for essential hypertension in two independent populations (Hani: odds ratio = 1.74, 95% confidence intervals 1.01–2.99, P = 0.046; Yi: odds ratio = 1.27, 95% confidence intervals 0.82–1.96, P = 0.277). Meta-analysis revealed that the C allele could significantly increase the risk of essential hypertension (odds ratio = 1.44, 95% confidence intervals 1.02–2.02, P = 0.037). Conclusion: Our findings suggest that rs387967 is associated with the susceptibility to essential hypertension in a Yi population and the tendency was replicated in systolic blood pressure and diastolic blood pressure detection. Meta-analysis revealed that C allele of rs2638360 could significantly increase the risk of essential hypertension. The two single nucleotide polymorphisms maybe play a role in the pathology of essential hypertension.

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Genetic polymorphisms of the angiotensin II type 1 receptor gene and diastolic heart failure

Abstract: We identified risk-conferring genetic variants of the AGTR1 gene for DHF in a Chinese population.

Cited by 61 publications

References 28 publications

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure

Genetic variations in MOV10 and CACNB2 are associated with hypertension in a Chinese Han population

Polymorphisms within angiotensin II receptor type 1 gene associated with essential hypertension in Chinese Hani and Yi minorities

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