Angiotensin-converting enzyme gene D-allele and the severity of coronary artery disease

Vladeanu, Maria-Cristina; Bojan, Iris Bararu; Bojan, Andrei; Iliescu, Dan; Bădulescu, Oana Viola; Bădescu, Magda; Georgescu, Cătălina Arsenescu; Ciocoiu, Manuela

doi:10.3892/etm.2020.8978

Cited by 8 publications

(9 citation statements)

References 17 publications

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“…Similar results were reported by MM et al [ 46 ], which showed a significant correlation of ACE2-I/D genotypes with respect to age ( p < 0.035). On the other hand, there was a study done by Maria-Cristina Vladeanu et al [ 47 ] that reported no statistically significant differences. Moreover, the results showed that there is no association between ACE2-rs4646994 I/D genotypes and the gender of patients with a ( p < 0.33), and the majority of them were males.…”

Section: Discussionmentioning

confidence: 93%

Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression

et al. 2022

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Background: Experimental clinical and research studies demonstrated that the renin–angiotensin system (RAS) affects the pathogenesis of atherosclerosis and the prognosis of coronary heart disease (CHD). The results show that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. The aim of this study was to develop, optimize, and validate a direct T-ARMS-based PCR assay for the precise and rapid genotyping of ACE1-rs4646996 D>I and ACE2-rs4240157T>C and study their association with coronary artery disease susceptibility and progression. Methodology: This study included 149 consecutive coronary artery disease patients and 150 healthy controls. We utilized T-ARMS for the precise and rapid genotyping of ACE2-rs4240157; rs4646994. Results: Our results indicated that the ACE1-rs4646996 D>I genotypes observed between CAD cases and controls were statistically significant (p < 0.008) and, similarly, the ACE2-rs4240157T>C genotypes observed were significant (p < 0.0001). Moreover, the frequency of the D allele (ACE1-D>I) and C allele (ACE2-rs4240157T>C) was found to be higher among CAD patients than the HC. Our results indicated that in the codominant model, the ACE2-ID genotype was strongly associated with increased CAD susceptibility in a codominant model with an OR of 2.37, (95%) CI = (1.023–5.504), and p < 0.04. Similarly, the ACE2-DD genotype was strongly associated with an increased CAD susceptibility with an OR of 3.48, (95%) CI = (1.49 to 8.117), and p < 0.003. Similarly, in allelic comparison, the D allele was strongly associated with CAD susceptibility with an OR of 1.59, (95%) CI = (1.12–2.24), and p < 0.003. Our results revealed that there was a significant correlation between ACE2-I/D genotypes and hypertension, T2D, and obesity (p < 0.05). The results of ACE2 rs4240157 genotyping indicated a strong association in the codominant model with an increased CAD susceptibility with an OR of 3.62, (95%) CI = (2.027 to 6.481), and p < 0.0001. Similarly, in a dominant inheritance model, a strong association is observed between the ACE2 rs4240157 (CT+CC) genotype with an OR of 6.34, (95%) CI = (3.741 to 10.749), and p < 0.0001. In allelic comparison, the T allele was strongly associated with CAD susceptibility with an OR of 5.56, (95% CI = (3.56 to 7.17), and p < 0.0001. Similarly, our results revealed that there was a significant association of the ACE2-rs4240157T>C genotypes with Triglycerides (mg/dL), HDL-C (mg/dL), total Cholesterol (mg/dL), and C-reactive protein (mg/L) in CAD. Conclusion: It was indicated that the ARMS technique and MS-PCR assay proved to be fast, accurate, and reliable for ACE2-rs4240157T>C and ACE1-rs4646996 D>I, respectively, and can be used as a potential molecular tool in the diagnosis of genetic diseases in undeveloped and developing countries—where there might be a shortage of medical resources and supplies. ACE1-I>D genotypes were strongly associated with T2D, hypertension, and obesity (p < 0.002). Besides the ACE2-rs4240157 CT heterozygosity genotype, the T allele was strongly associated with CAD susceptibility. Future longitudinal studies in different ethnic populations with larger sample sizes are recommended to validate these findings

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Section: Discussionmentioning

confidence: 93%

Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression

et al. 2022

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“…Chen et al showed that acute coronary syndrome patients with the DD genotype have a 3.87-fold increased risk of stenosis in three coronary vessels, a 3.08-fold higher risk of stenosis of the left anterior descending artery, and a 3.07-fold higher risk of anterior wall infarction ( 6 ). Another study also indicated that the D allele was associated with the number of stenosed coronary arteries, especially its interaction with cardiovascular risk factors, such as sex (male), age (>65 years old), hypertension, diabetes, obesity, and smoking ( 7 ). In a group of 647 patients who underwent elective coronary angiography, Borzyszkowska et al found a significant association between the ACE DD genotype and the Gensini score in men with high total cholesterol, high LDL cholesterol, and low HDL cholesterol levels ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to environmental factors, genetic components have been revealed to be associated with the severity of CAD in AMI patients. Recent research has shown that CAD severity is influenced by variations in the angiotensin-converting enzyme ( ACE ) gene ( 6 , 7 ). ACE, an important component of the renin-angiotensin-aldosterone system, converts angiotensin I to angiotensin II and inactivates bradykinin via the kallikrein-kininogen system ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Association between ACE I/D genetic polymorphism and the severity of coronary artery disease in Vietnamese patients with acute myocardial infarction

Tran

Thai

et al. 2023

Front. Cardiovasc. Med.

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BackgroundThe severity of coronary artery disease is a prognostic factor for major adverse cardiovascular events in patients diagnosed with acute myocardial infarction. ACE I/D polymorphism is one of the genetic factors that may affect the severity of coronary artery disease. This study aimed to investigate the association between ACE I/D genotypes and the severity of coronary artery disease in patients with acute myocardial infarction.Materials and methodsA single-center, prospective, observational study was conducted at the Department of Cardiology and Department of Interventional Cardiology, Cho Ray Hospital, Ho Chi Minh City, Vietnam from January 2020 to June 2021. All participants diagnosed with acute myocardial infarction underwent contrast-enhanced coronary angiography. The severity of coronary artery disease was determined by Gensini score. ACE I/D genotypes were identified in all subjects by using the polymerase chain reaction method.ResultsA total of 522 patients diagnosed with first acute myocardial infarction were recruited. The patients' median Gensini score was 34.3. The II, ID, and DD genotype rates of ACE I/D polymorphism were 48.9%, 36.4%, and 14.7%, respectively. After adjusting for confounding factors, multivariable linear regression analysis showed that the ACE DD genotype was independently associated with a higher Gensini score compared with the II or ID genotypes.ConclusionThe DD genotype of the ACE I/D polymorphism was associated with the severity of coronary artery disease in Vietnamese patients diagnosed with first acute myocardial infarction.

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“…SARS-CoV infected patients often suffer from cardiac diseases as well as sudden death [121]. Amara et al, have shown that several risk factors had significant effects on CAD, including diabetes and dyslipidemia [122], in addition to gender, age, family history, smoking and genetic factors [123,124].…”

Section: Covid-19 and The Cardiovascular Systemmentioning

confidence: 99%

“…The RAS plays a role in cardiovascular homeostasis and hemodynamics, the reason for which is the special interest that has been accorded to its role in developing CVD [120], mostly due to some allelic variants in gene encoding for the RAS components [122,127]. Some mutations in these genes might influence the initiation and the outcome of CAD [124]. Essential hypertension, for example, is related to some genetic mutations in RAS components, such as the AT1R gene, and to angiotensinogen (AGT) M235T and ACE I/D polymorphisms [38].…”

Section: Covid-19 and The Cardiovascular Systemmentioning

confidence: 99%

The Renin-Angiotensin System: A Key Role in SARS-CoV-2-Induced COVID-19

et al. 2021

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The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin–angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.

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Angiotensin-converting enzyme gene D-allele and the severity of coronary artery disease

Cited by 8 publications

References 17 publications

Association between ACE I/D genetic polymorphism and the severity of coronary artery disease in Vietnamese patients with acute myocardial infarction

The Renin-Angiotensin System: A Key Role in SARS-CoV-2-Induced COVID-19

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