The Impact of Pentraxin 3 Serum Levels and Angiotensin-Converting Enzyme Polymorphism on Pulmonary Infiltrates and Mortality in COVID-19 Patients.

OBJECTIVES: The aim of this study was to examine the impact of the pentraxin 3 (PTX3) serum level and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on the severity of radiographic pulmonary infiltrates and the clinical outcomes of COVID-19. METHODS: The severity of COVID-19 pulmonary infiltrates was evaluated within a week of admission by analyzing chest X-rays (CXR) using the modified Brixia (MBrixa) scoring system. The insertion (I)/deletion (D) polymorphism of the ACE gene and the serum levels of PTX3 were determined for all patients included in the study. RESULTS: This study included 80 patients. Using a cut-off serum level of PTX3 ≥ 2.765 ng/mL, the ROC analysis (AUC 0.871, 95% CI 0.787-0.954, p < 0.001) showed a sensitivity of 85.7% and specificity of 78.8% in predicting severe MBrixa scores. Compared to ACE I/I polymorphism, D/D polymorphism significantly increased the risk of severe CXR infiltrates, OR 7.7 (95% CI: 1.9-30.1), and p = 0.002. Significant independent predictors of severe CXR infiltrates include hypertension (OR 7.71), PTX3 (OR 1.20), and ACE D/D polymorphism (OR 18.72). Hypertension (OR 6.91), PTX3 (OR 1.47), and ACE I/I polymorphism (OR 0.09) are significant predictors of poor outcomes. CONCLUSION: PTX3 and ACE D/D polymorphism are significant predictors of the severity of COVID-19 pneumonia. PTX3 is a significant predictor of death.

Impact of ACE I gene insertion/deletion, A-240T polymorphisms and the renin-angiotensin-aldosterone system on COVID-19 disease.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19. METHODS: Our preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19. RESULTS: Our study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels. CONCLUSIONS: Although there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response. CLINICAL TRIAL REGISTRATION: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020.

Investigation of Serum Angiotensin-Converting Enzyme (ACE) Concentration and ACE Gene Polymorphism in Patients With SARS-CoV-2 Pneumonia Admitted to the Emergency Department.

Background This study seeks to investigate the distribution of the angiotensin-converting enzyme (ACE) gene polymorphism and serum levels in patients with viral pneumonia and predict which polymorphism will lead to severe progression of the disease. Methodology The serum ACE levels and ACE gene polymorphisms were successfully evaluated with respect to subsequent viral pneumonia using records of 100 patients with viral pneumonia and 100 healthy controls. Results ACE serum concentration was statistically significantly elevated. ACE serum concentration with a cut-off value of ≥5,256.05 pg/mL had 85.3% sensitivity and 83.2% selectivity. In addition, patients with ACE genotype D/D were 0.08 times more likely to manifest severe lung involvement than those with I/I, and patients with the I/D genotype were 0.02 times more likely than their counterparts with I/I. The computed tomography findings of the patients revealed that ACE serum concentration was significantly effective in discriminating between mild and moderate-to-severe lung involvement. No significant difference was observed between the blood parameters and ACE genotype distributions. Conclusions I/D polymorphism likely affects the expression of the ACE gene and/or the function of the angiotensin I converting enzyme. The D/D genotype is associated with vessel wall thickness and higher blood pressure. Strong evidence was found between D/D and I/D genotypes in the patient cohort concerning genotypes and ACE serum concentration. Further analysis showed that ACE serum levels were more elevated in the D/D genotype compared to the I/D genotype in the patient cohort.

SNPs of ACE1 (rs4343) and ACE2 (rs2285666) genes are linked to SARS-CoV-2 infection but not with the severity of disease.

COVID-19 and the renin-angiotensin system (RAS) are linked by angiotensin-converting enzyme 2 (ACE2), a key enzyme in RAS that has been validated as a SARS-CoV-2 receptor. Functional ACE1/ACE2 gene polymorphisms may lead to the imbalance between ACE/ACE2 ratio and thus generating RAS imbalance that is associated with higher degrees of lung damage in ARDS that may contribute to the COVID-19 infection outcome. Herein, we investigated the role of RAS gene polymorphisms, ACE1 (A2350G) and ACE2 (G8790A) as risk predictors for susceptibility and severity of COVID-19 infection. A total of 129 included: negative controls without a history of COVID-19 infection (n = 50), positive controls with a history of COVID-19 infection who were not hospitalized (n = 35), and patients with severe COVID-19 infection who were hospitalized in the intensive care unit (n = 44). rs4343 of ACE and rs2285666 of ACE2 were genotyped using PCR-RFLP method. Our results indicated that susceptibility to COVID-19 infection was associated with age, GG genotype of A2350G (Pa = 0.01; OR 4.7; 95% CI 1.4-15.1 and Pc = 0.040; OR 2.5; 95% CI 1.05-6.3) and GG genotype of G8790A (Pa = 0.044; OR 6.17; 95% CI 1.05-35.71 and Pc = 0.0001; OR 5.5; 95% CI 2.4-12.4). The G allele of A2350G (Pa = 0.21; OR 1.74; 95% CI 0.73-4.17 and Pc = 0.007; OR 2.1; 95% CI 1.2-3.5) and G allele of G8790A (Pa = 0.002; OR 4.26; 95% CI 1.7-10.65 and Pc = 0.0001; OR 4.7; 95% CI 2.4-9.2) were more frequent in ICU-admitted patients and positive control group. Also lung involvement due to COVID-19 infection was associated with age and the comorbidities such as diabetes. In conclusion, our findings support the association between the wild genotype (GG) of ACE2 and homozygote genotype (GG) of ACE1 and sensitivity to COVID-19 infection, but not its severity. However, confirmation of this hypothesis requires further studies with more participants.

Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.

Accumulating data has shown a contribution of the renin-angiotensin system in COVID-19 pathogenesis. The role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID-19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case-control study and assessed the impact of ACE I/D genotype in COVID-19 disease prevalence and severity. In 81 COVID-19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID-19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0-fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266-2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051-1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID-19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID-19 patients compared to healthy individuals and set the grounds for large-scale studies assessing ACE genotype-based optimized therapies with ACE inhibitors and angiotensin receptor blockers.

Muscle Work and Its Relationship with ACE and ACTN3 Polymorphisms Are Associated with the Improvement of Explosive Strength.

BACKGROUND: The potential influence of genetics in athletic performance allows the search for genetic profiles associated with muscular work for the orientation of strength training and sports selection. The purpose of the study was to analyze four muscular exercises for effectiveness in improving explosive strength variables, associated to the genetics in Angiotensin Converting Enzyme (ACE) and α-actinin-3 (ACTN3) polymorphisms. METHODS: A randomized controlled trial was conducted on a sample of 80 subjects allocated into four groups: concentric muscle work (CMW), eccentric muscle work (EMW), concentric-eccentric muscle (C-EMW) work and isometric muscular work (IMW), by block and gender randomization. Vertical jump, long jump, power jump, and speed were measured to study explosive strength. Genotypic frequencies of ACE (rs4646994) and ACTN3 (rs1815739) were obtained by polymerase chain reaction. RESULTS: ACE gen showed significant improvements regarding the DD genotype in the Sargent test (p = 0.003) and sprint velocity test (p = 0.017). In the ACTN3 gene, the RR variable obtained improvement results with regard to RX and XX variables in long jump (p < 0.001), Sargent test (p < 0.001) and power jump (p = 0.004). CONCLUSIONS: The selected genes demonstrated an influence on the muscle work and the improvement in explosive strength variables with a decisive role regarding the type of muscle work performed.

Risk Assessment Using the Association Between Renin-Angiotensin Genes Polymorphisms and Coronary Artery Disease.

Coronary artery disease (CAD) is a multifactorial disease that involves genetic and environmental interaction. In addition to the well-known CAD risk factors, such as diabetes mellitus, hypertension, hyperlipidemia, and atherosclerosis, it has a genetic component that predisposes to its occurrence even in young people. One of the most commonly studied genes that increase the susceptibility to CAD is renin-angiotensin system (RAS) genes polymorphisms mainly angiotensin-converting enzyme gene (ACE) polymorphisms, angiotensinogen polymorphisms, angiotensin- II type 1 receptor gene polymorphisms, and many other genes. These genetic polymorphisms have a direct association with CAD development or indirect association through causing atherosclerosis and hypertension which, in turn, are complicated by CAD later on. The difference between genetic mutations and polymorphisms lies in the frequency of the abnormal genotype. If the frequency is 1% and more in the general population, it is called polymorphism and if it is less than 1%, then it is called a mutation. According to our findings, after thorough searching, which support the association of RAS genes polymorphisms with premature CAD, hypertension, hypertrophic cardiomyopathy, and atherosclerosis, we recommend additional studies in the form of clinical trials and meta-analyses aiming to create a specific diagnostic tool for CAD risk assessment and discovering the high-risk people as early as possible. Targeted gene therapy, being the future of medicine, needs to be taken into researchers' consideration. It can have promising results in these cases.

Role of Angiotensin-Converting Enzyme (ACE) gene polymorphism and ACE activity in predicting outcome after acute myocardial infarction.

BACKGROUND: The Ace polymorphism had shown association with ACE activity, premature atherosclerosis, myocardial infarction, LV dysfunction, LV remodelling, severity and extent of CAD and mortality after MI. Though ACE I/D polymorphism has been reported to be associated with various cardiovascular diseases it remained a controversial risk factor and studies have presented conflicting results. This study was designed to determine the association between ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and acute STEMI in Indian population and to determine its influence on outcome after acute MI. MATERIALS AND METHODS: We investigated 934 patients diagnosed with acute STEMI who underwent thrombolysis. ACE I/D polymorphism was detected by polymerase chain reaction and ACE activity was measured in 615 patients. RESULTS: The prevalence of DD, ID, and II genotypes in our study group were 41.97%, 34.36%, and 23.66% respectively. The ACE polymorphism was not significantly associated with the type of myocardial infarction, the LV ejection fraction, the number of vessels diseased and patency of the vessel after thrombolysis. The polymorphism had no influence on in hospital mortality (P = 0.453). The ACE activity also showed no influence on in hospital mortality (P = 0.482). The age > 60 years, Male gender, occluded artery and severe LV dysfunction (LVEF < 35%) were predictors of in-hospital mortality on multivariate regression analysis. CONCLUSION: There was no differences among ACE (I/D) polymorphism observed in STEMI population. Neither ACE I/D polymorphism nor ACE activity predicted in-hospital mortality inpatients admitted with acute STEMI.

ACE I allele is associated with more severe portal hypertension in patients with liver cirrhosis: A pilot study.

BACKGROUND: In liver cirrhosis, the renin-angiotensin-aldosterone system is involved in the pathogenesis of portal hypertension. Its effector, angiotensin II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are affected by I/D polymorphism of its gene, with alleles I and D being associated, respectively, with lesser and greater activity of the enzyme. In cirrhotic patients carrying the ACE I allele, an increased risk for gastro-oesophageal varices was observed. AIM: The aim of our study was to evaluate whether ACE I/D polymorphism influenced portal pressure. METHODS: Fifty-one consecutive cirrhotic patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver function tests, upper endoscopy, and hepatic venous pressure gradient measurement (HVPG) were performed in all patients. RESULTS: The presence of the ACE I allele was associated with a higher HVPG value (18.7±6.4 vs 10.3±6.3mmHg; P<.001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P<.05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P<.05). No significant differences were found between patients with and those without the ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic encephalopathy. CONCLUSION: ACE I/D polymorphism seems to influence the severity of portal hypertension and the risk of variceal bleeding in liver cirrhosis, regardless of the severity of liver disease.

Angiotensin-Converting Enzyme (ACE) D Allele as a Risk Factor for Increase Serum Interleukin-6 and Interleukin-8 in Psoriasis Patients.

BACKGROUND: Psoriasis is a chronic, recurrent inflammatory skin disease. It is characterised by autoimmune, environmental factors and complex genetic disorder. AIM: To explore the role of IL-6, IL-8, and ACE I/D polymorphism in the pathogenesis of Psoriasis and investigation of the relationship between ACE polymorphism and occurrence of psoriasis. PATIENTS AND METHODS: In this study, we took 73 psoriasis patients and 47 healthy patients as a control. These two groups subjected to analysis for ACE gene I/D polymorphism by PCR and biochemical methods. RESULTS: The serum levels of ACE, IL-8 and IL-6 were statistically significantly higher in psoriasis patients compared to healthy subjects (P < 0.001). ID and DD polymorphism were more common in psoriasis patients than healthy subjects. Also, D allele was significantly over-represented in patients compared to controls (52.7% Vs 35.1%). CONCLUSION: ACE gene polymorphism might grant susceptibility to develop psoriasis.

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke.

PURPOSE: Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke. METHOD: This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR). RESULT: In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (ß = -0.232, p = 0.024). CONCLUSION: This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.

Deletion Polymorphism of Angiotensin-Converting Enzyme Gene Is Associated with Low Muscle Mass in Elderly People in Jakarta, Indonesia.

Decline in muscle mass due to aging is a growing public health problem as it contributes to a decreased capacity for independent living among elderly people. A clear understanding of genetic factors is important, as it is known that angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism affects muscle mass, although the findings are frequently heterogeneous. This study was conducted to determine the association between ACE I/D polymorphism and muscle mass in elderly people. A total of 130 elderly people were recruited from nursing homes in Jakarta. Anthropometric components affecting the muscle mass were examined. Cross-sectional analyses were performed to compare data using t-test, ANOVA and ANCOVA, and linear regression. Genotyping of the ACE I/D polymorphisms was performed by PCR methods, and muscle mass was evaluated by BIA. Genotype distribution counts II 65.38%, ID 13.85%, and DD 20.77% were not consistent with the Hardy-Weinberg equilibrium (χ² = 22.2, df = 2; p < 0.01). Individuals with the DD genotype showed lower muscle mass that was significantly different compared to the muscle mass in individuals with the II/ID genotype (II 16.14 ± 0.38, ID 15.71 ± 0.59; DD 13.95 ± 0.61 kg), after adjusting for % fat as a covariate. The linear regression analysis showed that age, gender, weight, height, nutritional status, protein content, and waist, hip, and calf circumference were significant contributors to muscle mass. In the multivariate analysis, adjusted age and gender significantly correlated with muscle mass, with r² = 0.98, by the likelihood ratio test (p < 0.01). The genotype variability accounted for 2.65% of the DD genotype. This study showed that in an elderly population in Jakarta, the DD genotype was associated with low muscle mass. This result suggests the role of nutritional status as a potential mediator in the association between ACE gene and muscle mass.

Preeclampsia is associated with ACE I/D polymorphism, obesity and oxidative damage in Mexican women.

OBJECTIVE: This study sought to determine whether the angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism, obesity and oxidative damage are risk factors for the development of preeclampsia in Mexican women. STUDY DESIGN: A total of 66 women with preeclampsia (PE) and 37 women with normal pregnancies (NP) were included in the study. DNA was extracted from whole blood, and the ACE I/D polymorphism was evaluated by polymerase chain reaction. ACE activity and oxidative damage were assessed in plasma. The intergroup comparisons were analyzed by an analysis of variance (ANOVA) with post hoc tests. Hardy-Weinberg equilibrium (HWE) was tested by x2 analysis, odds ratios (OR) were calculated as a measure of the degree of relative risk of preeclampsia, and for correlations, we used Spearman's correlation coefficient. RESULTS: The frequency of the DD genotype was higher in PE (34.84%) than NP (10.82%). The OR of the DD genotype and D allele were associated with a 4.4-fold (CI=95% 2.24-14) and 3-fold (CI=95% 1.69-5.62) increased risk of developing PE, respectively. Major ACE activity in the DD genotype and obesity were features of the PE group; oxidative damage to proteins and a reduction in the activity of the antioxidant system showed a correlation with BMI (p<0.01). CONCLUSION: Our results suggest that ACE I/D polymorphism, high ACE activity, body mass index and oxidative damage may play key roles in the pathogenesis of PE in the Mexican population. Furthermore, these findings could be used as predictive factors of PE.

Impact of I/D polymorphism of ACE gene on risk of development and course of chronic obstructive pulmonary disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) affects more than 10% of the world's population over 40 years of age. The main exogenous risk factor is cigarette smoking; however, only 20% of smokers develop COPD, indicating that some other factors, e.g. genetic, may play an important role in the disease pathogenesis. Recent research indicates that ACE (angiotensin-converting enzyme) may be a susceptibility gene for asthma or COPD. The aim of our study was to determine the influence of I/D (insertion/deletion) polymorphism of the ACE gene (AluYa5, rs4646994) on the risk and course of COPD. MATERIAL AND METHODS: We investigated ACE I/D polymorphism in 206 COPD and 165 healthy Caucasian subjects. RESULTS: In the generalized linear model (GLZ) analysis of the influence of selected factors on presence of COPD we found a significant independent effect for male sex (repeatedly increases the risk of COPD, OR = 7.7, p = 0.049), as well as smoking or lower body mass index, but only in combination with older age (OR = 0.96, p = 0.003 and OR = 1.005, p = 0.04 respectively). Interestingly, analysis of factors which may influence the risk of a higher number of exacerbations demonstrated that occurrence of DD genotype, but only in men, is associated with a lower risk (OR = 0.7, p = 0.03) of this complication. CONCLUSIONS: We suggest that ACE may not be a susceptibility gene for the origin of COPD but a disease-modifying gene. Since the impact of I/D polymorphism of the ACE gene on COPD risk is moderate or negligible, other molecular changes, that will help predict the development of this disease, should still be sought.

Lack of Association between Angiotensin Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage in Saudi Arabia.

BACKGROUND: An insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene has been associated with recurrent miscarriage (RM) in several populations. We initiated this study to determine the association, if any, between the I/D polymorphism of ACE gene and RM in Saudi females. METHOD: This study was conducted on 61 Saudi females suffering from RM (mean age: 34.1±6.2 years; range 15-45) attending clinics at King Khalid University Hospital, and 59 age matched females who had at least 2 children, as controls. Blood samples were drawn in EDTA tubes by venipuncture. DNA was extracted using the Puregene DNA purification kits. Insertion/Deletion (I/D) polymorphism of ACE gene was investigated by amplifying the genomic DNA by PCR using gene-specific primers. A single 190 bp or 490 bp band was obtained in the homozygous cases for the D allele or I allele, respectively, while the presence of both 190 and 490 bp bands indicated heterozygosity (ID). STATISTICAL ANALYSIS: Deviation from Hardy-Weinberg equilibrium was determined (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl). A standard chi-square (χ2) test was used for comparing the genotype and allele frequencies in the two groups and Students't' test and χ2 test were employed to compare values between the two groups. P<0.05 was considered statistically significant. RESULTS: The frequencies of DD, ID, and II genotypes were 56.7%, 29.5% and 4.9%, respectively, in females with RM and 54.2%, 42.3% and 3.3% respectively in the control group, but the difference was not statistically significant. CONCLUSION: In some populations, meta-analyses showed an association between I/D polymorphism and RM risk, and the D allele was implicated as an increased risk factor for RM. However, this association was not apparent in the Saudi females.

Genetic ACE I/D polymorphism and recurrence of atrial fibrillation after catheter ablation.

BACKGROUND: The angiotensin-converting enzyme (ACE) deletion allele, ACE D, is associated with increased cardiac ACE activity, cardiac fibrosis, and adverse outcomes in cardiovascular disease and has been linked with failure of antiatrial fibrillation (anti-AF) drug treatment. This study tested the hypothesis that the ACE gene insertion/deletion polymorphism associates with AF recurrence after catheter ablation. METHODS AND RESULTS: In 238 consecutive patients (69% male; mean age, 58±11 years) undergoing catheter ablation of paroxysmal (59%) or persistent (41%) AF, the ACE insertion/deletion polymorphism was genotyped using polymerase chain reaction. After a blanking period of 3 months, AF recurrence (defined as any atrial arrhythmia lasting ≥30 s) was detected using serial 7-day Holter ECG recordings after 3, 6, and 12 months. AF recurrence was observed in 39% and was associated with persistent AF, longer history of AF, previous antiarrhythmic drug use, previous use of diuretics, increased left atrial diameter, increased left ventricular end-diastolic diameter, additional linear ablation lesions, and ACE DD polymorphism. In multivariable analysis, left atrial diameter (odds ratio, 1.111; 95% confidence interval, 1.040-1.187; P=0.002) and ACE DD genotype (odds ratio, 2.251; 95% confidence interval, 1.056-4.798; P=0.036) remained predictors for AF recurrence. CONCLUSIONS: Left atrial enlargement and the ACE DD polymorphism are predictors for AF recurrence after catheter ablation. The association between the ACE DD polymorphism and AF recidivism supports the use of genetic data for predicting response to AF therapies and highlights the role of fibrosis in AF development.

Association of angiotensin-converting enzyme activity and polymorphism with echocardiographic measures in familial and nonfamilial hypertrophic cardiomyopathy

Angiotensin-converting enzyme (ACE) activity and polymorphism contribute significantly to the prognosis of patients with cardiomyopathy. The aim of this study was to determine the activity and type of ACE polymorphism in patients with familial and nonfamilial hypertrophic cardiomyopathy (HCM) and to correlate these with echocardiographic measurements (echo-Doppler). We studied 136 patients (76 males) with HCM (69 familial and 67 nonfamilial cases). Mean age was 41 ¡À 17 years. DNA was extracted from blood samples for the polymerase chain reaction and the determination of plasma ACE levels. Left ventricular mass, interventricular septum, and wall thickness were measured. Mean left ventricular mass index, interventricular septum and wall thickness in familial and nonfamilial forms were 154 ¡À 63 and 174 ¡À 57 g/m2 (P = 0.008), 19 ¡À 5 and 21 ¡À 5 mm (P = 0.02), and 10 ¡À 2 and 12 ¡À 3 mm (P = 0.0001), respectively. ACE genotype frequencies were DD = 35%, ID = 52%, and II = 13%. A positive association was observed between serum ACE activity and left ventricular mass index (P = 0.04). Logistic regression showed that ACE activity was twice as high in patients with familial HCM and left ventricular mass index ¡Ý190 g/m2 compared with the nonfamilial form (P = 0.02). No other correlation was observed between ACE polymorphisms and the degree of myocardial hypertrophy. In conclusion, ACE activity, but not ACE polymorphisms, was associated with the degree of myocardialhypertrophy in the patients with HCM.

Implication of Angiotensin Converting Enzyme Gene Polymorphism on Renal Progression of Primary Nephrotic Syndrome in Children / 대한신장학회잡지

Human angiotensin converting enzymcC4CE) gene displays an insertion/deletion polymorphism in 16 intron, and three genotypes are determined by presence or absence of a 287-bp fragment of DNA; II, ID and DD genotype. DD genotype has been suggested as a risk factor of various cardiovascular diseases and chronic nephropathies such as IgA nephropathy and diabetic nephropathy. This study was designed to investigate if the ACE polymor-phism is related to the clinical and pathologic findings of minimal change nephrotic syndrome(MCNS) and focal segmental glomerulosclerosis(FSGS) in children. Ninety children with primary nephrotic syndrome(MCNS and steroid responsive nephrotic syndrome : 68 cases, FSGS; 22 cases) and 97 healthy normal controls were examined. The genotype for the polymorphism was determined by PCR method. The distribution of ACE genotypes in primary nephrotic syndrome(II 28.6%, ID 53.8%, DD 17.6%) was not different from that in controls(II 39.2%, ID 41.2%, DD 29.6%). The IJ genotype was more frequent in FSGS(II 64.7%, ID 23.5%, I)D 11.8%) than in MCNS and steroid responsive nephrotic syndrome(I 20.3%, ID 60.8%, DD 18.9%, p<0.03). The ACE genotypes were not associated either with frequency of relapse in MCNS or steroid responsive nephrotic syndrome or with presence of hypertension, responsiveness to steroid therapy and progression of renal dysfunction in FSGS. We concluded that deletion polymorphism of ACE gene is not associated with increased risk for renal progression in children with primary nephrotic syndrome.

An I/D Polymorphism in Angiotensin-Converting Enzyme Gene in Myocardial Infarction

BACKGROUND: The angiotensin-converting enzyme(ACE) plays an important role in cardiovascular disease by production of angiotensin and degradation of bradykinin. Cloning of ACE gene revealed an insertion/deletion(I/D) polymorphism according to the presence/absence of a 287 base pair fragment in the 16th intron of ACE gene, and the ACE polymophism was associated with ACE activity. The genotype DD was identified as a risk factor for myocardial infarction in several studies. We analyzed the ACE I/D polymorphism in 62 patients with myocardial infarction and 67 normal subjects. METHODS: Genomic DNA from peripheral blood was amplified by polymerase chain reaction and characterized by three ACE genotypes; two insertion alleles(genotype II), two deletion alleles(genotype DD) and heterogenous alleles(genotype ID). ACE activity was determined by spectrophotometric method utilizing the synthetic substrate. RESULTS: There was no significant difference in ACE polymorphism between patients and normal subjects. But, the frequency of genotype DD was significantly increased in the low-risk group of patients compared with the high-risk group. The multi-vessel disease was more strongly associated with genotype DD, but there was no statistical significance. The ACE activity was strongly associated with ACE polymorphism with the activity being highest in genotype DD. There was no significant difference between patients and control subjects of the same genotype. CONCLUSION: There was no significant difference in ACE polymorphism between patients and normal subjects. The frequencies for genotype II, ID, DD were 0.328, 0.537, 0.134, respectively in normal subjects. There was high frequency of genotype II compared with Caucasians. A deletion polymorphism(genotype DD) may increase the risk for myocardial infarction in lowrisk group, and the serum ACE activity was correlated with three genotypes.