Angiotensin-Converting Enzyme Gene Polymorphism and Carotid Artery Wall Thickness

Sayed‐Tabatabaei, Fakhredin A.; Houwing-Duistermaat, Jeanine J.; Duijn, Cornelia M. van; Witteman, Jacqueline C. M.

doi:10.1161/01.str.0000077926.49330.64

Cited by 85 publications

(64 citation statements)

References 44 publications

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“…23,24 In the general population, the ACE I/D D allele has been related to cardiovascular mortality in several meta-analyses, although such association was not duplicated by others. [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.…”

Section: Survival Free Of Death From Cardiovascular Eventsmentioning

confidence: 97%

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: 97%

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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“…36,37 Furthermore, several studies and metaanalyses of ACE and Atg polymorphisms demonstrate significant ethnic heterogeneity, with stronger associations of the D allele or DD genotype in Asian compared to Caucasian populations. 17,18,38 It is also possible given the retrospective study design that there may have been some selection bias due to decreased survival in patients with genotypes associated with higher RAS activity. This has been previously suggested in both a predialysis and dialysis population.…”

Section: Ras Gene Polymorphisms and Lupus Nephritismentioning

confidence: 99%

Renin–angiotensin system gene polymorphisms predict the progression to renal insufficiency among Asians with lupus nephritis

et al. 2005

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The renin-angiotensin system (RAS) is a strong candidate as a mediator for the development and progression of lupus nephritis (LN). We performed an ethnically stratified analysis of 642 systemic lupus erythematosus (SLE) patients to determine whether various functional RAS gene polymorphisms are associated with SLE renal outcomes. Patients were genotyped for two angiotensin-converting enzyme (ACE) gene polymorphisms: Alu insertion/deletion (I/D) and 23 949 (CT) 2/3 , and for two angiotensinogen (Atg) gene polymorphisms: M235T and C-532T. Multivariate analyses demonstrated associations between the ACE I/D, ACE (CT) 2/3 and Atg C-532T functional polymorphisms and LN among Asians. In stratified analyses among LN cases according to high vs low glomerular filtration rate (GFR), associations remained significant for the ACE D (odds ratio (OR) 5.9, P ¼ 0.001) and (CT) 2 (OR 6.2, P ¼ 0.001) alleles among Asian subjects with low GFR. Lastly, we found allelic dosedependent associations between the ACE I/D (P ¼ 0.003), ACE (CT) 2/3 (P ¼ 0.005) and Atg M235T (P ¼ 0.04) polymorphisms, and GFR analyzed as a continuous variable among Asians. These findings suggest a significant role for ACE and Atg gene sequence variation and severity of LN among Asians with SLE.

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“…The insertion or deletion (I/D) of a 287-bp-long Alu repeat element in the intron 16 of this gene was proven associated with the altered levels of circulating ACE enzyme (Rigat et al 1990) as well as with cardiovascular pathophysiologies (Cambien et al 1992;Jeunemaitre et al 1992a;Keavney et al 1995). Some of the conducted studies showed positive association of DD genotype and increased risk of myocardial infarction and atherosclerosis (AgerholmLarsen et al 2000;Sayed-Tabatabaei et al 2003). However, a great number of studies, including metaanalyses, associating ACE I/D with hypertension (HT), cardiomyopathy, and coronary arthery disease showed controversial results (Jeunemaitre et al 1992bLindpaintner et al 1995;Staessen et al 1997;Sharma 1998;Dikmen et al 2006;Xu et al 2008;VaisiRaygani et al 2010).…”

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confidence: 99%

Angiotensin-converting enzyme deletion allele is beneficial for the longevity of Europeans

Petranović

Škarić‐Jurić

Narančić

et al. 2011

AGE

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The human angiotensin converting enzyme (ACE) gene is one of the most investigated candidate genes for cardiovascular diseases (CVD), but the understanding of its role among the elderly is vague. Therefore, this study focuses at: (a) testing the association of ACE polymorphism with CVD risk factors among the elderly, and (b) detecting the possible unequal distribution of ACE genotypes between senescent and younger segments of the European populations. The association of ACE I/D polymorphism with CVD health status [hypertension (HT), obesity, dislypidemia] in 301 very old subjects (88.2±5 years; F/M=221/80) was tested by means of logistic regression analysis. The meta-analysis of D allele frequency in general vs. elderly (80+ years) groups was conducted using all publicly available data for European populations comprising both age cohorts. Multiple multinomial logistic regression revealed that within this elderly sample, age (younger olds, 80-90 years), female sex (OR=3.13, 95% CI= 1.59-6.19), and elevated triglycerides (OR=2.53, 95% CI=1.29-4.95) were positively associated with HT, while ACE polymorphism was not. It was also established that the DD genotype was twice as high in 80+ cohort compared to general population of Croatia (p<0.00001). This trend was confirmed by the metaanalysis that showed higher D allele frequencies in olds from nine of ten considered European populations (OR=1.19, 95% CI=1.08-1.31). The data in elderly cohort do not confirm previously reported role of ACE DD genotype to the development of HT. Moreover, meta-analysis indicated that ACE D allele has some selective advantage that contributes to longevity in majority of European populations.

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Angiotensin-Converting Enzyme Gene Polymorphism and Carotid Artery Wall Thickness

Cited by 85 publications

References 44 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

Renin–angiotensin system gene polymorphisms predict the progression to renal insufficiency among Asians with lupus nephritis

Angiotensin-converting enzyme deletion allele is beneficial for the longevity of Europeans

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