ACE DD Research Articles

P137 ACE AND ACE 2 ENZYMES POLYMORPHISM IN DIFFERENT CLINICAL COVID-19 MANIFESTATIONS IN HOSPITAL-ADMITTED PATIENTS

Introduction: The affinity of SARS-CoV-2 for the Angiotensin Converting Enzyme 2 (ACE2), component of the Renin-Angiotensin System (RAS), is responsible for the COVID-19 virus internalization, and the ACE and ACE2 genes polymorphisms may contribute for the disease outcome. Objective: To correlate the I/D ACE and the G8790A ACE2 polymorphisms and their enzymatic activity to the virus susceptibility and the disease's clinical severity. Methods: 408 patients from Alfa Hospital, Recife – PE, were assessed. ACE activity was measured by fluorometry and the real time PCR technique was used to assess ACE's DD, ID, and II polymorphisms. Results: 71.9% of COVID-19 affected patients needed hospitalization, with 56.8% being male ranging from 40 to 59 years old. In the positive group, there were more patients with blood hypertension (80.6% vs 19.4%), diabetes (88.2% vs 11.8%), and obesity (87.5% vs 12.5%). ACE activity was higher in positive patients (46.5 vs 43.5 nmol/mL/min), with greater prevalence of the DD genotype, 85.6% of frequency between negatives and positives. When it comes to DD genotype, ACE activity was higher (48.5 nmol/mL/min). In patients with blood hypertension, ID genotype was more frequent than the DD one. Conclusion: The interaction of genetic and risk factors may lead to different COVID-19 symptomatology. The scientific literature states that ACE polymorphism may contribute for the development of blood hypertension, as the DD genotype being the susceptible one for developing cardiovascular complications by the higher concentration of Angiotensin II converted from Angiotensin I by ACE, increasing the hypertensive effects in relation to the anti-hypertensive ones of Angiotensin 1-7. The positive group showed more incidence of blood hypertension, diabetes and obesity, as well as higher frequency of the DD genotype, which is already established in literature to lead to blood hypertension due to increased ACE activity. From the observed in these results, it is suggested a correlation between ACE polymorphism and the factors that may aggravate COVID-19

Association of variants in AGTR1, ACE, MTHFR genes with microalbuminuria and risk factors for the onset of diabetic nephropathy in adolescents with type 1 diabetes in the population of Serbia.

Genetic studies may provide valuable information about patients who are at high risk of developing diabetes nephropathy. Before the appearance of albuminuria, there are genetic mutations that can predispose the development of kidney disease. The study included 130 adolescents with type 1 diabetes. Patients were divided into two groups according to the presence of microalbuminuria. This study was performed to examine clinical and laboratory differences between adolescents with type 1 diabetes with and without microalbuminuria and the distribution of the ACE, AGTR1, and MTHFR gene polymorphisms. The mean microalbuminuria in the first group 6.41±7.35 significantly differs from the second group 0.82±0.48 (p<0.001). HbA1c, 24-hour proteinuria, and day-time systolic blood pressure were significantly higher in the MA group (p<0.05). Smaller systolic blood pressure percentage nocturnal decline was observed in the microalbuminuric group (p 0.030). The frequencies of the ACE DD, ID, and II genotypes were 12.5%, 50.0%, and 37.5%, respectively, among T1D patients with MA, and 19.3%, 56.1%, 24.6%, in the control group without MA (P = .510). The frequencies of the AGTR1 AA, AC, and CC genotypes were 62.5%, 25.0%, and 12.5% among TID patients with MA, and 49.1%, 43.9%, 8.0%, in the group without MA (p 0.326). The frequencies of the MTHFR CC, CT and TT genotypes were 37.5%, 50.0%, 12.5% among TID patients with MA, and 37.7%, 45.6%, 16.7% in the group without MA (p 0.901). Our data suggest that common variants in the AGTR1, ACE, and MTHFR genes are not strongly associated with diabetic nephropathy in our patients with type 1 diabetes.

The Predisposition for Type 2 Diabetes Mellitus and Metabolic Syndrome.

Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are diseases caused by the interaction of genetic and non-genetic factors. Therefore, the aim of our study was to investigate the association between six common genetic polymorphisms and T2DM and MetS in males. A total of 120 T2DM, 75 MetS, and 120 healthy controls (HC) were included in the study. ACE ID, eNOS 4a/b, ATR1 A1166C, OXTR (A>G), SOD1 +35A/C, CAT-21A/T gene polymorphisms were genotyped by PCR or PCR-RFLP techniques. T2DM was diagnosed at an earlier age compared to MetS (54 vs 55 years old, p=0.0003) and the difference was greater in carriers of the OXTR G allele (54 vs 56 years old, p=0.0002) or both OXTR G and eNOS b alleles (54 vs 56, p=0.00016). The SOD1 AA genotype (O.R.=0.11, p=0.0006) and the presence of both ACE I and OXTR1 A (O.R.=0.39, p=0.0005) alleles revealed to be protective for T2DM. SOD1 AA and AC genotypes were protective factors for triglyceride (p=0.0002 and p=0.0005, respectively) and HDL cholesterol (p=0.0002 and p=0.0004, respectively) levels in T2DM patients. ACE DD was identified more frequently in hypertensive T2DM patients (O.R.=3.77, p=0.0005) and in those who reported drinking alcohol (p=0.0001) comparing to HC and T2DM patients who did not drink alcohol, respectively. We observed that T2DM patients who reported drinking alcohol had an increased frequency of ACE DD and eNOS bb (p<0.0001), or ACE DD and OXTR G (p<0.0001) compared to non-drinkers. No gene polymorphisms were associated with MetS.

Strong association between angiotensin-converting enzyme gene InDel polymorphism and COVID-19 diseases

Background and ObjectivesThe COVID-19 pandemic that emerged in China in late 2019 and spread rapidly around the world. There is evidence that COVID-19 infection can be influenced by genetic variations in the host. The aim of this study was to investigate the association between ACE InDel polymorphism and COVID-19 in Northern Cyprus. Patients and methodsThis study included 250 patients diagnosed with COVID-19 and 371 healthy controls. Genotyping for the ACE InDel gene polymorphism was performed by polymerase chain reaction. ResultsThe frequency of ACE DD homozygotes was significantly increased in COVID-19 patients compared to the control group (p=0.022). The difference in the presence of the D allele between the patient and control groups was statistically significant (57.2% and 50.67%, respectively, p<0.05). Individuals with the genotype II were found to have a higher risk of symptomatic COVID-19 (p=0.011). In addition, chest radiographic findings were observed more frequently in individuals with the genotype DD compared to individuals with the genotypes ID and II (p=0.005). A statistically significant difference was found when the time of onset of symptoms for COVID-19 and duration of treatment were compared with participants’ genotypes (p=0.016 and p=0.014, respectively). The time of onset of COVID-19 was shorter in individuals with the genotype DD than in individuals with the genotype II, while the duration of treatment was longer. ConclusionIn conclusion, the ACE I/D polymorphism has the potential to predict the severity of COVID-19.

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

The 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. A 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. A 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. The 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.

Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.

Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop severe COVID-19. We conducted a systematic review of current evidence to investigate the association of genetic variants of these genes with the susceptibility to virus infection and patient prognosis. We systematically searched Medline, Embase and The Cochrane Library for articles published until May 2022, and included observational studies covering genetic association of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes with COVID-19 susceptibility or prognosis. We evaluated the methodological quality of included studies, and pooled data as convenient in meta-analysis (MA). Odds ratio (OR) values and 95% confidence intervals were calculated. We included 35 studies (20 on ACE, 5 each on IFITM3, TMPRSS2, TNFα), enrolling 21,452 participants, of them 9401 were COVID-19 confirmed cases. ACE1 rs4646994 and rs1799752, ACE2 rs2285666, TMPRSS2 rs12329760, IFITM3 rs12252 and TNFα rs1800629 were identifies as common polymorphisms. Our MA showed an association between genetic polymorphisms and susceptibility to SARS-CoV-2 infection for IFITM3 rs12252 CC (OR 5.67) and CT (OR 1.64) genotypes. Furthermore, MA uncovered that both ACE DD (OR 1.27) and IFITM3 CC (OR 2.26) genotypes carriers had a significantly increased risk of developing severe COVID-19. These results provide a critical evaluation of genetic polymorphisms as predictors in SARS-CoV-2 infection. ACE1 DD and IFITM3 CC polymorphisms would lead to a genetic predisposition for severe lung injury in patients with COVID-19.

Association between ACE I/D gene polymorphism and coronary artery lesion characteristics in patients with acute myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background Acute myocardial infarction (AMI) remains a public health issue with high morbidity and mortality rates and significantly reduces patients' health-related quality of life. The identification of factors influencing coronary artery lesion characteristics in patients with AMI can contribute to the strategy of primary and secondary prevention for AMI. Purpose This study was aimed to investigate the ACE I/D genotype rate and its relationship with coronary artery lesion characteristics in AMI patients. Methods This study was conducted with the prospective cross-sectional method among AMI patients admitted to the Department of Cardiology and Department of Interventional Cardiology, Cho Ray Hospital from January 1, 2020 to June 30, 2021. The minimum sample size of this study was 163 patients. The ACE I/D genotype was determined at the Center for Molecular Biomedicine. Results During the study period, a total of 522 AMI patients were recruited at the Department of General Cardiology and Department of Interventional Cardiology. The mean age of the AMI patients was 63.9±11.7 and the age group 45-64 accounted for the most (46.4%). Males were predominant (71.5%). 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. The ACE DD genotype was not associated with the location and number of diseased coronary arteries but was associated with the severity of coronary artery disease. Multivariable linear regression analysis showed that along with the Killip class, the ACE DD genotype was independently associated with a higher Gensini score compared with the II or ID genotype. Conclusions This has been the first study in Vietnam demonstrated the association between ACE I/D gene polymorphism and coronary artery lesion characteristics in patients with AMI. The ACE I/D gene polymorphism may be considered for testing to contribute to the comprehensive assessment and aggressive treatment of AMI patients.

Strong association between angiotensin-converting enzyme gene InDel polymorphism and COVID-19 diseases

Background and ObjectivesThe COVID-19 pandemic that emerged in China in late 2019 and spread rapidly around the world. There is evidence that COVID-19 infection can be influenced by genetic variations in the host. The aim of this study was to investigate the association between ACE InDel polymorphism and COVID-19 in Northern Cyprus. Patients and methodsThis study included 250 patients diagnosed with COVID-19 and 371 healthy controls. Genotyping for the ACE InDel gene polymorphism was performed by polymerase chain reaction. ResultsThe frequency of ACE DD homozygotes was significantly increased in COVID-19 patients compared to the control group (p=0.022). The difference in the presence of the D allele between the patient and control groups was statistically significant (57.2% and 50.67%, respectively, p<0.05). Individuals with the genotype II were found to have a higher risk of symptomatic COVID-19 (p=0.011). In addition, chest radiographic findings were observed more frequently in individuals with the genotype DD compared to individuals with the genotypes ID and II (p=0.005). A statistically significant difference was found when the time of onset of symptoms for COVID-19 and duration of treatment were compared with participants’ genotypes (p=0.016 and p=0.014, respectively). The time of onset of COVID-19 was shorter in individuals with the genotype DD than in individuals with the genotype II, while the duration of treatment was longer. ConclusionIn conclusion, the ACE I/D polymorphism has the potential to predict the severity of COVID-19.

Abstract P256: Higher Angiotensin Converting Enzymes Activities Are Observed In Covid-19 Positive Volunteers.

The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, Angiotensin Converting Enzyme 2 (ACE2). The depletion of the biological functions of ACE2, due to the internalization of the receptor along with SARS-CoV-2, leads to impairment of Renin Angiotensin System (RAS), which can contribute to COVID-19 pathogenesis. In addition, genetic differences in RAS may be associated with more severe symptoms and complications observed in COVID-19 patients. This study aims to perform a comparative analysis between COVID-19 positive patients and uninfected individuals, to correlate such disease profiles with ACE I/D (Insertion/Deletion) and ACE2 G8790A polymorphisms, and their enzymatic activities. The anthropometric, demographic, clinical and cardiovascular parameters of 764 individuals from Ipaussu/SP (Brazil) were evaluated. ACE and ACE2 activities were measured by fluorometric assays, and assessment of both enzymes polymorphisms was performed by PCR. In this cohort, 35,2% (269 of 764) the volunteers were positive for COVID-19. The prevalence of COVID-19 was higher among women (67%) and individuals aged between 18 and 49 years. Also, comorbidities as obesity and arterial hypertension were more frequent in the positive group, when considered individuals under 60 years old. Higher ACE and ACE2 enzymatic activities were observed in positive group (46.4 vs 41.6 and 11.3 vs 8.5, respectively). Individuals with ID genotype in the positive group presented higher ACE activity compared to individuals with same genotype in control group (46.9 vs 41.7). In the positive group, ACE activity was increased in the DD (54.5) when compared to ID (46.9) and II (37.9) genotypes. No significant differences related to ACE2 activity and polymorphism were observed. ACE/ACE2 activity ratio was higher in the COVID-19 negative group (4.7 vs 3.7). The increased ACE activity for the DD genotype was in line with the literature data for hypertension and cardiovascular diseases. We can suggest a synergic effect between ACE DD genotype and COVID-19 infection enhancing ACE activity, what may contribute to pro-inflammatory phenotype and more severe symptoms of COVID-19.

Effect of ACE, ACE2 and CYP11B2 gene polymorphisms and noise on essential hypertension among steelworkers in China: a case\u2013control study

BackgroundPrevious studies on the relationship between ACE I/D, ACE2 G8790A and CYP11B2-344T/C gene polymorphisms and essential hypertension (EH) were inconsistent. Moreover, few studies have reported the combined effect of these gene polymorphisms and noise exposure on EH. The purpose of this study was to explore the combined and separate effects of ACE I/D, ACE2 G8790A and CYP11B2-344T/C gene polymorphisms and noise on EH among steelworkers.MethodsA case–control study was conducted on 725 male workers between March 2014 and July 2014 in the Tangsteel Company, China. The noise exposure of the workers were measured. Logistic regression and crossover analysis were used to analyse the effects of the interactions on the EH among steelworkers. GMDR was used to determine the best combination model of gene–noise interactions.ResultsMultivariate logistic regression showed that noise exposure increased the odds of EH, and the OR is 1.52 (95% CI 1.04–2.22). The risk of having EH for ACE I/D DD genotype carriers was 1.99 times that for II genotype carriers (95% CI 1.14–3.51). There was a negative additive interaction between ACE2 G8790A and CYP11B2-344T/C on EH (U3 = − 2.221, P = 0.026, and S = 0.128) and a positive multiplicative interaction between ACE I/D and CYP11B2-344T/C on essential hypertension (P = 0.041). In addition, there was no significant gene–noise interaction model through the GMDR method after adjusting the confounders.ConclusionsThe ACE DD genotype may make men susceptible to EH. Simultaneously carrying the DD genotype of ACE I/D and the TC genotype of CYP11B2-344T/C increased the risk of EH.

Can a genetic profile be related to performance in young talent track and field athletes? A pilot study

Aim: This study analyzed the influences of ACE and ACTN3 gene variants in sprinters, jumpers, and endurance young athletes of track and field. Methods: 36 school-level competitors of both sex (15 girls and 21 boys; aged 16.4 ± 1.2 years; training experience 4 ± 1.2 years) practitioners of different sport disciplines (i.e., sprint, jump, and endurance athletes) participated in the study. The deoxyribonucleic acid (DNA) was extracted from peripheral blood using a standard protocol. Anthropometric measurements, 30 m sprint, squat jump (SJ), and maximal oxygen uptake (VO2max) tests were measured. Results: Genotype distribution of the ACE and ACTN3 genes did not differ between groups. In ACE DD and ACTN3 RX genotypes, the SJ test was bigger in sprinters and jumpers than in the endurance runners. In contrast, when analyzing the ACE ID genotype, sprinters had higher SJ than endurance athletes. Moreover, in the ACE DD genotype, the sprinters and jumpers’ athletes had lower time in 30 m tests compared to endurance runners. However, the ACE ID and ACTN3 RX genotypes was greater aerobic fitness in endurance runners than in jumpers’ athletes. Conclusion: Although the genetic profile is not a unique factor for determining athletic performance, the ACE DD and ACTN3 RX genotypes seem to favor athletic performance in power and sprint versus endurance sports. Thus, this study evidenced that assessing genetic variants could be used as an auxiliary way to predict a favorable profile for the identification of young talents of track and field.

Influence of ACE and ACTN3 genes polymorphisms on cardiovascular adaptation in female football players

The aim of study was to investigate distribution of ACE and ACTN3 gene polymorphisms in young female footballers and to test association of common gene polymorphisms with body composition, arterial blood pressure and ECG screening variables. A group of 45 white, healthy, adolescent female elite footballers (FG) and 60 sedentary female controls (CG) enrolled in this study. HRM method has been developed to differentiate between variant alleles of ACE and ACTN3 genes. No significant difference was found in the ACE and ACTN3 genotypes or allele frequencies distribution between FG and CG (p&gt;0.05). Also, neither insertion in the ACE gene, nor nonsense mutation in the ACTN3 gene had a significant effect on resting BP and ECG parameters. Cardiovascular adaptation to intensive physical activity in FG is manifested as lowered resting systolic and diastolic blood pressure (lower 18 and 11 percentiles, respectively). Footballers with ACE DD and ACTN3 XX polymorphisms had higher values of Sokolow-Lyon voltage for LV hypertrophy, but without statistically significance (p=0.61 and 0.2, respectively). Interpretation of the effect of specific genes with presumed large effect on sport performance, should be cautious, especially in team sports with a mixed type of physical activity, such as football.

Genetic correlates of creativity in military personnel under extreme conditions of the Arctic Zone of the Russian Federation: a pilot study

BACKGROUND: The ability of a person in the process of active activity to adapt to changing environmental conditions is largely related to his creative potential. Creativity, like other physical and mental personality traits, has its own genetic base, which has not been sufficiently studied to date. Certain genes involved in this process are regularly described. The search for an association with new candidate genes for the creative potential of practically healthy, young respondents selected for work in the extreme conditions of the North is extremely important in the selection of people for work and service in difficult conditions. AIM: Search for the correlation of candidate gene polymorphism and the psychological state of the examined. MATERIALS AND METHODS: The psychological block of the pilot study included determining the degree of creativity, as well as the degree of tension of key psychological defense mechanisms. All the techniques used within its framework are part of the standard psychodiagnostic tools that have been tested in domestic conditions. Genotyping was performed by real-time PCR, determining the corresponding alleles of candidate genes, and then the data were compared by the method of analysis of variance. RESULTS: As candidate genes, we selected the angiotensin-converting enzyme gene, the serotonin 2A receptor gene, the neurotrophic factor BDNF, and alpha-actinin-3. According to the literature, all these genes are associated with the ability to adapt and / or psychotic states, which suggests their possible connection with creativity. The most interesting results are associated with the polymorphism of the BDNF gene: respondents with the BDNF Val/Val genotype are characterized by the maximum level of creativity and the minimum level of intensity of basic psychological defenses and coping strategies by types of distancing, as well as seeking social support. On the contrary, their maximum level is associated with the Met/Met genotype. Thus, it has been reliably shown that optimal adaptation to extreme external conditions is most likely to be ensured genetically by the presence of the Val / Val genotype, and psychologically by enhanced use of creative ability. The respondents with the ACTN3 RX genotype (with increased cold resistance) are characterized by a minimum level of creativity, and those with the RR genotype its maximum level. It is also shown that respondents with the ACE DD genotype are characterized by a minimum level of creativity. There were no associations with creativity with the serotonin 2A receptor gene polymorphism. CONCLUSIONS: The totality of the results obtained as a result of this pilot study allows us to consider a systematic study of creative ability and its molecular biological correlates to be correct and constructive for the development of a fundamental problem of the interaction of molecular biological and psychological mechanisms that provide active adaptation, as well as very expedient for solving the complex. scientific and applied tasks for the selection and correction of the state of persons directed to work in special and / or extreme conditions.

ACE Insertion/Deletion gene polymorphism aassociations in STEMI Patients

Abstract Objective ACE Insertion/deletion (I/D) polymorphism has been reported to be associated with various cardiovascular conditions, however its impact in patients with AHF remains controversial. This study aimed to analyze ACE I/D distribution, rate of acute heart failure (AHF) and survival in ST segment elevation myocardial infarction (STEMI) patients. Methods Genomic DNA from 245 STEMI patients and 87 healthy control subjects were analyzed by single polymerase chain reaction method. Based on the ACE I/D genotype STEMI patients were divided with AHF/no AHF, and then - for preserved/reduced ≤40% left ventricle (LV) ejection fraction (EF) to investigate the frequency of the mutant allele D. Results ACE gene polymorphism analyses revealed that D allele had been found more often in STEMI patients than in controls (84.1 vs. 72.4%). The frequency of II, ID, and DD genotypes in STEMI patients was 27.6%, 52.9% and 19.5% compared to 15.9%, 54.3% and 29.8%, respectively in controls with a significant difference in mutant homozygous genotype. Distribution of I/D ACE gene variants among AHF cases vs no AHF, showed similar frequency of II allele (15.8 vs 13.5%), ID allele (54.9 vs 52.8%) and DD allele (29.3 vs 33.7% respectively). In patients with preserved EF there was not statistical significance among different alleles with and without AHF. However, ACE DD polymorphism has been found in AHF patients with reduced EF significantly more often (50.0 vs 30.5%; p&amp;lt;0.05) in compare to AHF patients with preserved EF. Finally, cardiovascular death among all STEMI patients during 3-year follow up was more frequent in patients with DD allele (17.7% vs 5.7% with II and vs 9.9% with ID allele). Conclusion Presented results confirmed ACE DD polymorphism to be associated with higher rate of cardiovascular death and presence of AHF with reduced LV EF in STEMI patients. Future studies are needed to evaluate importance of ACE DD polymorphism in order to find optimal treatment strategies and to prevent negative outcomes in those patients. Funding Acknowledgement Type of funding sources: None.

ACE gene I/D polymorphism and severity of SARS-CoV-2 infection in hospitalized patients: a meta-analysis

Background: Hypertension and type 2 diabetes increase the risk of severe SARS-CoV-2 infection. On the other hand, homozygous ACE deletion polymorphism (DD) has been associated with these two diseases and risk of acute respiratory distress syndrome. The aim of the study was to conduct a meta-analysis of the association between ACE gene I/D polymorphism (DD, II and DI) and severity of SARS-CoV-2 infection in hospitalized patients. Material and methods: We searched PubMed, EMBASE and Google Scholar for studies published between January 2020 and April 2021. We included case-control studies evaluating the association between ACE I/D and severity of SARS-CoV-2 infection in hospitalized patients, were there was sufficient genotype or allele frequency data to calculate IRR (incidence rate ratio) and 95% confidence intervals (CIs). Results: Five studies were included (mean age 58.5 years and 61% men), combining to a total of 786 patients. Four studies were conducted in Caucasians. Overall, patients who had homozygous co-dominance genotype DD were at 47% higher risk of severe COVID-19 compared with II or ID (IRR: 1.47; 95% CI: 1.15–1.89; p = 0.002). Conclusions: The ACE DD genotype may confer a greater risk of severe COVID-19 in hospitalized patients. Further studies including more diverse ethnic groups are necessary to fully establish this association.

A Study on the Association of Age, Gender and ACE I/D Polymorphism with Cardiovascular Risk Factors (CRFs) among Urban Population of Chandigarh, India

Cardiovascular diseases (CVDs) are multifactorial and predisposed by several risk factors. CVDs prevalence is attributed to cardiovascular risk factors (CRFs) such as hypertension, obesity, diabetes, ageing, gender and genetics. The specificity of CRFs to the habitat and lifestyle modification has differential CVDs outcomes. In the present cross-sectional study, we aimed at finding the prevalence of CRFs in an urban population. We also assessed the role of ACE I/D polymorphism, age and gender in CRFs susceptibility. Forty-four adult subjects, permanent residents of Chandigarh, India, were recruited in the present study. Anthropometric, physiological and demographic data were collected and analyzed. More than half of the subjects were having obesity and high blood pressure. Hyperglycemia was present in 43.9% of the subjects. Among ACE I/D genotypes, DD (45.5%) was followed by II (31.8%) and ID (22.7%), with a significant deviation from Hardy Weinberg Equilibrium. The high trends of CRFs depict that cardiovascular disease risk is very high in the present population of Chandigarh, India. The age might be one factor for this surge as subjects &gt;45 years displayed enhancement in combined CRFs. Urbanization might be another possible reason for CRFs surge. Gender and ACE I/D polymorphism was not associated with CRFs in the present study. Though their trend exhibited a possible association, the ACE DD genotype has the lowest frequency among combined CRFs and females have a high frequency of CRFs. The most critical point of this study is the alarming/exponential increase in CRFs in Chandigarh. A study with bigger sample size is warranted regarding CRFs to identify the reasons for their surge in Chandigarh, India.

ACE DD polymorphism in severe COVID-19

ACE DD polymorphism in severe COVID-19

The association of the ACTN3 R577X and ACE I/D polymorphisms with athlete status in football: a systematic review and meta-analysis

ABSTRACT The aim of this review was to assess the association of ACTN3 R577X and ACE I/D polymorphisms with athlete status in football and determine which allele and/or genotypes are most likely to influence this phenotype via a meta-analysis. A comprehensive search identified 17 ACTN3 and 19 ACE studies. Significant associations were shown between the presence of the ACTN3 R allele and professional footballer status (OR = 1.35, 95% CI: 1.18–1.53) and the ACE D allele and youth footballers (OR = 1.18, 95% CI: 1.01–1.38). More specifically, the ACTN3 RR genotype (OR = 1.48, 95% CI: 1.23–1.77) and ACE DD genotype (OR = 1.29, 95% CI: 1.02–1.63) exhibited the strongest associations, respectively. These findings may be explained by the association of the ACTN3 RR genotype and ACE DD genotype with power-orientated phenotypes and the relative contribution of power-orientated phenotypes to success in football. As such, the results of this review provide further evidence that individual genetic variation may contribute towards athlete status and can differentiate athletes of different competitive playing statuses in a homogenous team-sport cohort. Moreover, the ACTN3 R577X and ACE I/D polymorphisms are likely (albeit relatively minor) contributing factors that influence athlete status in football.

Evaluation of the effect of serum cystatin-C and ACE I/D and ACE G2350A polymorphisms on kidney function among hypertensive sewage workers.

Cadmium (Cd) as nephrotoxicant metal exerts its potent effect mainly on renal tubules disturbing its functions. A cross-sectional study was conducted on 55 sewage workers occupationally exposed to Cd and 50 control subjects. The study aimed to assess the effect of low-level Cd exposure on blood pressure and renal function in terms of serum cystatin-C levels. The associations between genetic polymorphisms of ACEI/D and ACE G2350A and hypertension and tubular injury among workers were studied. We analyzed blood and urine Cd concentration (U-Cd), serum cystatin-C, ACE I/D polymorphisms, and ACE G2350A, and blood pressure was measured. Results recorded a significant rise in serum and U-Cd and cystatin-C levels in sewage workers compared with controls. Significant distribution in genotype frequency of ACE I/D and ACE G2350A gene was detected. An association in DD genotype of ACE I/D with a rise in serum and U-Cd was observed in workers. In wild type genotype GG of ACE G2350A gene, a significant rise in serum cystatin-C levels and diastolic pressure was found while in heterozygote genotype GA significant rise in U-Cd levels was detected. Also, the association of AA genotype of ACE G2350A gene with a significant rise in serum and U-Cd and cystatin-C levels was shown among workers compared with control groups. Our findings indicated an association of ACE DD polymorphism in conjugation with GG genotype of ACE2 with hypertension and tubular injury in sewage workers.

Analysis of the Association Between Polymorphisms within PAI-1 and ACE genes and Ischemic Stroke Outcome After rt-PA Therapy.

Treatment of Ischemic stroke (IS) in acute phase is based on the use of thrombolytic rt-PA therapy. We aimed to determine whether different alleles and genotypes of I/D ACE gene and 4G/5G PAI-1 gene polymorphisms may influence outcome of rt-PA therapy in patients with IS and the occurrence of haemorrhagic transformation (HT). Our study included 94 consecutive patients with IS treated with rt-PA. Modified Rankin Scale (mRS) at 3rd month after IS was used to determine the stroke outcome, with scores 0-1 defining the favourable outcome, and scores 2-6 defining poor outcome. Genotypisation of the ACE-1 I/D polymorphism was performed by polymerase chain reaction and of the PAI-1 4G/5G polymorphism by polymerase chain reaction - restriction fragment length analysis. Regarding PAI-I 4G/5G polymorphism, 44 patients (46.8%) were heterozygotes, and the number of 4G/4G and 5G/5G homozygotes was the same - 25 each (26.6%). Number of heterozygotes for the ACE I/D polymorphism was 54 (57.4%), 9 patients (9.6%) had II, and 31 (33%) DD genotypes. A favourable outcome was recorded in 26 (28.0%) and the poor outcome in 67 (72.0%) patients. Favourable and poor outcome groups did not differ significantly in PAI-1 4G/5G and ACE I/D polymorphisms genotype or allele frequencies. There was a statistically significant difference in the occurrence of HT between patients with ACE II and patients with ACE ID or DD genotypes (p=0.035). Results of our study suggest that stroke patients with ACE II genotype, treated with rt-PA, may be at risk of HT.