Genetic Variations in the Human Angiotensin-ConvertingEnzyme 2 and Susceptibility to Coronavirus Disease-19.

Background: Health and economies are both affected by the coronavirus disease-19 (COVID-19) global pandemic. Angiotensin-converting enzyme 2 (ACE2) is a polymorphic enzyme that is a part of the renin-angiotensin system, and it plays a crucial role in viral entry. Previous investigations and studies revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ACE2 have a considerable association. Recently, ACE2 variants have been described in human populations in association with cardiovascular and pulmonary conditions. In this study, genetic susceptibility to COVID-19 in different populations was investigated. Methods and Results: We evaluated the identified variants based on the predictive performance of 5 deleteriousness-scoring methods and the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. The results indicated 299 variants within the ACE2 gene. The variants were analyzed by different in-silico analysis tools to assess their functional effects. Ultimately, 5 more deleterious variants were found in the ACE2 gene. Conclusions: Collecting more information about the variations in binding affinity between SARS-CoV-2 and host-cell receptors due to ACE2 variants leads to progress in treatment strategies for COVID-19. The evidence accumulated in this study showed that ACE2 variants in different populations may be associated with the genetic susceptibility, symptoms, and outcome of SARS-CoV-2 infection.

Correlation between the insertion-deletion variant of the angiotensin-converting enzyme gene and various classes of heart failure.

The angiotensin-converting enzyme (ACE) genetic variation for insertion/deletion (I/D) is located at the 16th intron of the ACE gene. A number of studies investigated the homozygous deletion genotype of ACE and its association with cardiovascular diseases. However, ACE's genetic variation and its association with heart failure (HF) is yet to be confirmed. We examined the possibility of the association between the ACE I/D gene variant with the severity of HF. The ACE genotypes were determined by polymerase chain reactions using samples derived from 150 patients with HF and 90 healthy subjects which were age and gender-matched. These patients included those of all four of the New York Heart Association (NYHA) classes. Echocardiography was performed on all HF patients and ejection fraction (EF), left ventricular systolic and diastolic diameters were measured. The HF patients were redistributed to systolic where EF is equal and less than 45% and non-systolic HF where EF is more than 45%. We demonstrate a statistically significant difference in DD genotype in NYHA class IV in comparison to the control group. The values of odds ratio (OR) (95%CI) of the DD genotype (DD vs ID and II) were 3.37 (1.01-11.19) (p value = 0.039) and the OR (95%CI) of the D allele (D vs I) was 2.55 (0.98-6.65) (p value = 0.049). Higher frequencies of D allele compared to I allele is linked to severity of HF. DD variant of the ACE gene is associated with NYHA class IV heart failure. This could have a profound impact on risk stratification and prognosis of HF in the management of this condition.

The angiotensin-converting enzyme I/D polymorphism does not impact training-induced adaptations in exercise capacity in patients with stable coronary artery disease.

Systematic exercise training effectively improves exercise capacity in patients with coronary artery disease (CAD), but the magnitude of improvements is highly heterogeneous. We investigated whether this heterogeneity in exercise capacity gains is influenced by the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. Patients with CAD (n = 169) were randomly assigned to 12 weeks of exercise training or standard care, and 142 patients completed the study. The ACE polymorphism was determined for 128 patients (82% males, 67 ± 9 years). Peak oxygen uptake was measured before and after the 12-week intervention. The ACE I/D polymorphism frequency was n = 48 for D/D homozygotes, n = 61 for I/D heterozygotes and n = 19 for I/I homozygotes. Baseline peak oxygen uptake was 23.3 ± 5.0 ml/kg/min in D/D homozygotes, 22.1 ± 5.3 ml/kg/min in I/D heterozygotes and 23.1 ± 6.0 ml/kg/min in I/I homozygotes, with no statistical differences between genotype groups (P = 0.50). The ACE I/D polymorphism frequency in the exercise group was n = 26 for D/D, n = 21 for I/D and n = 12 for I/I. After exercise training, peak oxygen uptake was increased (P < 0.001) in D/D homozygotes by 2.6 ± 1.7 ml/kg/min, in I/D heterozygotes by 2.7 ± 1.9 ml/kg/min, and in I/I homozygotes by 2.1 ± 1.3 ml/kg/min. However, the improvements were similar between genotype groups (time × genotype, P = 0.55). In conclusion, the ACE I/D polymorphism does not affect baseline exercise capacity or exercise capacity gains in response to 12 weeks of high-intensity exercise training in patients with stable CAD.Clinical trial registration: www.clinicaltrials.gov (NCT04268992).

Pharmacogenetics of angiotensin modulators according to APOE-ϵ4 alleles and the ACE insertion/deletion polymorphism in Alzheimer's disease.

OBJECTIVE: In Alzheimer's disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-ß by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-ß-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the ACE insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (APOE)-ϵ4 carrier status and blood pressure response to angiotensin modulators. METHODS: Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking APOE-ϵ4 carrier status and genotypes of the ACE insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs. RESULTS: For 193 patients (67.4% women, 53.4% APOE-ϵ4 carriers), the ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (p = 0.281), while arterial hypertension was prevalent in 80.3% (n = 124 used an ACEi, n = 21 used an ARB). ARBs benefitted mostly APOE-ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted APOE-ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The ACE insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations. CONCLUSION: Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.

Correlation between angiotensin-converting-enzyme 2 gene polymorphisms and systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is a disease with cardiovascular impairment and polymorphisms of the gene coding of angiotensin-converting-enzyme 2 (ACE2) may account for its development. Three single nucleotide polymorphisms of ACE2 (C>G rs879922, G>A rs2285666 and A>G rs1978124) were found to increase the risk for development of arterial hypertension (AH) and cardiovascular (CVS) diseases in different ethnicities. We investigated associations of polymorphisms rs879922, rs2285666 and rs1978124 with the development of SSc. METHODS: Genomic DNA was isolated from whole blood. Restriction-fragment-length polymorphism was used for genotyping of rs1978124, while detection of rs879922 and rs2285666 was based on TaqMan SNP Genotyping Assay. Serum level of ACE2 was assayed with commercially available ELISA test. RESULTS: 81 SSc patients (60 women, 21 men) were enrolled. Allele C of rs879922 polymorphism was associated with significantly greater risk for development of AH (OR=2.5, p=0.018), but less frequent joint involvement. A strong tendency to earlier onset of Raynaud's phenomenon and SSc was seen in carriers of allele A of rs2285666 polymorphism. They had lower risk for development of any CVS disease (RR=0.4, p=0.051) and tendency to less frequent gastrointestinal involvement. Women with genotype AG of rs1978124 polymorphism had significantly more frequent digital tip ulcers and lower serum level of ACE2. CONCLUSIONS: Polymorphisms of ACE2 may account for the development of AH and CVS disorders in SSc patients. Strong tendencies to more frequent occurrence of disease specific characteristics distinct to macrovascular involvement will require further studies evaluating significance of ACE2 polymorphisms in SSc.

Strong association between angiotensin-converting enzyme gene InDel polymorphism and COVID-19 diseases / Fuerte asociación entre el polimorfismo InDel del gen de la enzima convesiva de angiotensina y las enfermedades por COVID-19

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. (AU)

Antecedentes y objetivosLa pandemia de COVID-19 surgió en China a fines de 2019 y se extendió rápidamente por todo el mundo. Existe evidencia de que la infección por COVID-19 puede verse influenciada por variaciones genéticas en el huésped. El objetivo de este estudio fue investigar la asociación entre el polimorfismo ACE InDel y COVID-19 en el norte de Chipre.Pacientes y métodosSe incluyeron 250 pacientes diagnosticados de COVID-19 y 371 controles sanos. El genotipado del polimorfismo del gen ACE InDel se realizó mediante reacción en cadena de la polimerasa.ResultadosLa frecuencia de homocigotos ACE DD aumentó significativamente en pacientes con COVID-19 en comparación con el grupo de control (p=0,022). La diferencia en la presencia del alelo D entre los grupos de pacientes y control fue estadísticamente significativa (57,2% y 50,67%, respectivamente, p<0,05). Las personas con el genotipo II tenían un mayor riesgo de COVID-19 sintomático (p=0,011). Además, los hallazgos radiográficos de tórax se observaron con mayor frecuencia en individuos con el genotipo DD en comparación con los individuos con los genotipos ID y II (p=0,005). Se encontró una diferencia estadísticamente significativa cuando se comparó el tiempo de aparición de los síntomas de COVID-19 y la duración del tratamiento con los genotipos de los participantes (p=0,016 y p=0,014, respectivamente). El tiempo de aparición de COVID-19 fue más corto en individuos con genotipoDD que en individuos con genotipoII, mientras que la duración del tratamiento fue más prolongada.ConclusionesEl polimorfismo ACE I/D podría predecir la gravedad de la COVID-19. (AU)

Single Nucleotide Variants (SNVs) of Angiotensin-Converting Enzymes (ACE1 and ACE2): A Plausible Explanation for the Global Variation in COVID-19 Prevalence.

Background: Although it is common knowledge that the coronavirus disease of 2019 (COVID-19) and other viral infections have an uneven impact globally, the reasons for this are still indistinct. The absence of equivalent capacities worldwide in screening, testing, and reporting of cases is one of the ideas put forward to explain this discrepancy. The molecular developments are noteworthy, particularly the role played by single nucleotide polymorphisms (SNPs) in ACEs (ACE1 and ACE2). The virus can enter the host cell thanks to the transmembrane protein ACE2, which is a homolog of ACE1. Objectives: With a focus on the I/D genotype of ACE1 and the rs2285666 SNV of ACE2, we elucidated the prevalence of SNPs in ACE1 and ACE2 in various geographic locations. We examined the relationship between these SNPs and the global patterns of COVID-19 prevalence. Methods: 66 of the 127 articles obtained using PubMed, Google Scholar, and Google directly conformed to the search terms; geographical distribution of viral infections, the prevalence of COVID-19, ACE1, ACE2, SNPs, and prevalence of the DD genotype, and rs2285666. Results: The DD genotype of ACE1 and the rs2285666 SNV of ACE2 are vital in their gene expression and contribute greatly to viral disease susceptibility, development, and severity. There was generally a high prevalence of the DD genotype in Europe and America, where COVID-19 had a more devastating effect than in Asia and Africa. The prevalence of the SNV rs2285666 varied in the following order: East Asia> South Asia >America>Europe >Africa. However, there were conflicting agreements in the association of rs2285666 with COVID-19 susceptibility and prevalence. Conclusion: The ACE1 DD genotype and COVID-19 prevalence have been positively linked in a number of studies. The ACE2 rs2285666 SNV, however, has yielded no definitive results. To determine the relationship between these SNVs and COVID-19 incidence, more research is required.

The effect of AT1R-1166A/C and AT2R-1675A/G polymorphisms on susceptibility to preeclampsia: A systematic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis is to investigate the association between Angiotensin II type 1 receptor (AT1R)-1166A/C, Angiotensin II type 2 receptor (AT2R)-1675A/G polymorphisms and susceptibility to preeclampsia (PE). METHODS: Online databases, including Web of Science, PubMed, EMBASE, CINAHL, CENTRAL, Scopus, Lilacs/SciELO, and Chinese National Knowledge Infrastructure, China Wan Fang, China Science and Technology Journal Database, were used to perform the literature search up to April 2022. The odds ratio (OR) and 95% confidence interval (CI) were used as effect size. The data was analyzed by Stata 15.0 software. RESULTS: According to the inclusion and exclusion criteria, a total of 22 case-control studies were identified, including 3524 cases and 6308 controls. Our meta-analysis showed that the AT1R -1166 A/C allele was significantly associated with susceptibility to PE (A vs C: OR = 0.82, 95% CI: 0.69-0.96, P = .013), and there was significant difference in recessive gene model (AA vs AC + CC: OR = 0.81, 95% CI: 0.67-0.97, P = .021). However, no association was found between AT2R-1675A/G polymorphism and susceptibility to PE. CONCLUSION: our meta-analysis suggested that AT1R-1166A/C polymorphism had an association with susceptibility to PE, but AT2R-1675A/G polymorphism had no association with susceptibility to PE.

Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism with susceptibility to prostate cancer: an updated meta-analysis.

OBJECTIVE: This meta-analysis aims to explore the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and susceptibility to prostate cancer (PCa). METHODS: We searched studies related to ACE I/D polymorphism and susceptibility to PCa through PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases from inception to June 1, 2022. Five gene models, including allelic, dominant, recessive, homozygote, and heterozygote models, were analyzed. The pooled odds ratio (OR) was calculated using Stata 15.0 software. Publication bias was judged by the funnel plot and Egger's test, with the robustness of the findings verified by sensitivity analysis. RESULTS: Eight published articles (including ten studies) were identified. The pooled results showed that ACE I/D locus polymorphism was significantly correlated with the risk of PCa under all gene models except for the heterozygous model (D vs. I: OR= 1.58, 95% CI: 1.14-2.21; DD vs. DI+II: OR=1.68, 95% CI: 1.11-2.54; DD+DI vs. II: OR=1.76, 95% CI: 1.11-2.80; DI vs. II: OR= 1.44, 95% CI: 0.99-2.10; DD vs. II: OR= 2.12, 95% CI: 1.15-3.93). Subgroup analysis based on genotype frequencies in the control group meeting Hardy-Weinberg equilibrium showed statistically significant differences in all gene models. The funnel plot and Egger's test indicated no publication bias. The sensitivity analysis verified the robustness of the conclusions obtained in this meta-analysis. CONCLUSION: ACE I/D locus polymorphism correlates to PCa risk. Allele D, genotype DD+DI, and DD at the ACE I/D locus increase susceptibility to PCa and can therefore serve as a potential diagnostic and screening molecular marker for PCa patients.

Biophysical and structural characterizations of the effects of mutations on the structure-activity relationships of SARS-CoV-2 spike protein.

Mutations on the spike (S) protein of SARS-CoV-2 could induce structural changes that help increase viral transmissibility and enhance resistance to antibody neutralization. Here, we report a robust workflow to prepare recombinant S protein variants and its host receptor angiotensin-convert enzyme 2 (ACE2) by using a mammalian cell expression system. The functional states of the S protein variants are investigated by cryo-electron microscopy (cryo-EM) and negative staining electron microscopy (NSEM) to visualize their molecular structures in response to mutations, receptor binding, antibody binding, and environmental changes. The folding stabilities of the S protein variants can be deduced from morphological changes based on NSEM imaging analysis. Differential scanning calorimetry provides thermodynamic information to complement NSEM. Impacts of the mutations on host receptor binding and antibody neutralization are in vitro by kinetic binding analyses in addition to atomic insights gleaned from cryo-electron microscopy (cryo-EM). This experimental strategy is generally applicable to studying the molecular basis of host-pathogen interactions.

Association of ACE2 Gene Variants with the Severity of COVID-19 Disease-A Prospective Observational Study.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), has triggered an enormous scientific response. Many studies have focused on understanding the entry of the SARS-CoV-2 virus into the host cell. The angiotensin-converting enzyme-2 (ACE2) is recognized as the host receptor used by SARS-CoV-2 to enter its target cells. Recent studies suggest that ACE2 gene polymorphisms might be candidates for genetic susceptibility to SARS-CoV-2 infection. The aim of this study is to evaluate the influence of ACE2 polymorphisms on COVID-19 disease risk and severity. In our study, we confirmed that there is a statistically significant increased risk of a more severe disease course of SARS-CoV-2 infection associated with the need for hospitalization in intensive care for patients with specific polymorphisms of the ACE2 gene. The most significant correlation was found for variant ACE2 rs2285666 (AA allele, OR = 2.12, p = 0.0189) and ACE2 rs2074192 (TT allele, OR = 2.05, p = 0.0016), and for ACE2 rs4646174 (GG allele, OR = 1.93, p = 0.0016), ACE2 rs4646156 (TT allele OR = 1.71, p = 0.008) and ACE2 rs2158083 (TT allele OR = 1.84, p = 0.0025). In conclusion, our findings identify that certain ACE2 polymorphisms impact the severity of COVID-19 disease independently of other well-known risk factors.

Association between Insertion-Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Treatment Response to Antipsychotic Medications: A Study of Antipsychotic-Naïve First-Episode Psychosis Patients and Nonadherent Chronic Psychosis Patients.

We investigated whether a functional insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) influenced antipsychotic treatment. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed patients' Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic-syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis. The ACE-I/D polymorphism was significantly associated with changes in PANSS psychopathology only (p < 0.05). Compared to ACE-II homozygous males, ACE-DD homozygous and ACE-ID heterozygous males manifested significantly greater decreases in PANSS positive score, PANSS excitement factor, and PANSS cognitive factor. ACE-DD homozygous females manifested higher decreases in PANSS depression factor compared to ACE-II homozygous and ACE-ID heterozygous females. The polymorphism's effect size was estimated as moderate to strong, while its contribution to the PANSS psychopathology ranged from ~5.4 to 8.7%, with the lowest contribution observed for PANSS positive score changes and the highest for PANSS depressive factor changes. Our results indicate that ACE-I/D polymorphism had a statistically significant but weak gender-specific impact on psychopathology data, and showed no association between ACE-I/D polymorphism and metabolic-syndrome-related parameters.

Angiotensin-converting enzyme 1 and voltage-gated potassium channel-interacting protein 4 gene polymorphisms in COVID-19 patients from east of Iran.

BACKGROUND: Coronavirus disease 2019(COVID-19), the infectious respiratory disease caused by a newly discovered pathogen (severe acute respiratory syndrome coronavirus 2), is a pandemic that places a burden on the health care system. Recently, most research on COVID-19 has emphasized its profound impact on specific regions and ethnic groups. A possible explanation for these variations in disease presentation and severity might be differences in the gene pool of populations. This study therefore attempted to clarify possible involvements of genetic factors affecting COVID-19 pathogenesis with a focus on voltage-gated potassium channel-interacting protein 4 (KCNIP4) and angiotensin-converting enzyme 1 (ACE1) gene polymorphisms. MATERIALS AND METHODS: In this case-control study, the polymorphisms were genotyped using PCR in 194 COVID-19 patients and 194 healthy controls. RESULTS: COVID-19 susceptibility and severity appeared to be unaffected by these polymorphisms. However, this study supported the relevance of ACE1 II genotype frequency to a decreased number of deaths due to the infection. We found that COVID-19 patients with the ACE1 II genotype have a statistically significant better chance of survival (p = 0.008). CONCLUSION: This study strengthens the idea that the ACE1 I/D polymorphism can be a novel prognostic factor indicating the outcome of COVID-19.

The association of angiotensin-converting enzyme gene polymorphism with respiratory distress syndrome in premature neonates.

BACKGROUND: There was a contradiction in the previous literature on whether the D/D genotype of angiotensinconverting enzyme (ACE) is a protective or risk factor for respiratory distress syndrome (RDS) in premature neonates. To solve this debate, we intended to examine the association between ACE gene polymorphism and RDS in premature neonates. METHODS: We enrolled a total of 100 premature neonates with gestational age below 37 weeks. They were divided into 2 groups, the case group included 50 premature neonates diagnosed with RDS. While the control group included 50 premature neonates with no signs of RDS. We assessed ACE gene polymorphism using polymerase chain reaction. All neonates underwent chest x-ray, echocardiography, and routine laboratory investigations. RESULTS: D/D and D/I genotypes were higher in the control group (48% and 50%) than in the case group (26% and 40%). Whereas, I/I genotype was lower in the control group (2%) than in the case group (34%) (p < 0.001). By counting D alleles among members of both groups, D-alleles were significantly higher in the control group (73%) than in the case group (46%) (p < 0.001). CONCLUSIONS: In premature neonates, D/D and D/I genotypes and D-alleles are protective factors for RDS. Whereas, I/I genotype and I-alleles are associated with the incidence of RDS with complications.

Association of Angiotensin-converting Enzyme Gene Polymorphism with Susceptibility to Asthma Disease in Western Iran.

Asthma is a complex disease caused by a combination of multiple genetic and environmental factors. Angiotensin-converting enzyme (ACE) is involved in the pathogenesis of asthma by inactivating bradykinin, substance P, and neurokinin A. It has been shown that the level of ACE variation in serum is associated with an insertion-deletion (I/D) polymorphism. So, this study aimed to investigate the association of these polymorphisms with asthma in western Iran. In this case-control study, 111 asthmatic patients as a case group and 80 healthy subjects as a control group were evaluated. The ACE gene polymorphism was determined by the PCR method. The relationship between genotypes done by the χ2 test and the relative risk of disease with genetic polymorphism (Odds Ratio) was performed using logistic regression. The frequency of I/D genotypes (included in II, ID, and DD) between patient and control groups had no significant difference. In addition, none of the genotypes in the patient and control groups show any significant differences between men and women. However, the frequency of ID and DD genotypes was considerably different between the male patient groups (over and under 40 years old). Hence, these genotypes are suggested to be a risk factor for asthma. The results of our study indicate that ACE gene polymorphism is not significantly associated with asthma in the west of Iran.

Genetic variations of renin-angiotensin and fibrinolytic systems and susceptibility to coronary artery disease: a population genetics perspective.

BACKGROUND: Genetic predisposition is an important risk factor in coronary artery disease (CAD).This study was conducted to determine the polymorphism frequencies of the plasminogen activator inhibitor-1(PAI-1) gene 4G/5G, angiotensin-converting enzyme (ACE) gene I/D, and angiotensin II type 1 receptor (AT1) gene A1166C genotypes and to examine the role of these polymorphisms in CAD. METHODS: Genomic DNAs obtained from 260 subjects (130 CAD patients and 130 control) were used in the study. ACE I/D and PAI-1 4G/5G polymorphism genotypes were determined using polymerase chain reaction (PCR) and electrophoresis. AT-1 A1166C polymorphism was determined using the PCR, restriction fragment length polymorphism (RFLP) and electrophoresis. The products amplified from AT1 gene by PCR were cut with HindIII restriction endonuclease and then analyzed by 2% agarose gel electrophoresis. The results were statistically analyzed with the chi-square test, Mann-Whitney U test, and independent two-sample t-test. RESULTS: Allele frequencies showed statistically significant differences between the patient and control groups. There was no statistically significant difference in ACEI/D genotype frequencies between the twogroups. Likewise, no statistically significant difference was found in the AT1 A1166C genotype frequencies; however, a statistically significant difference was found in allele frequencies. The PAI-1 4G/5G genotype frequency was significantly higher in the patient group. CONCLUSIONS: While there is a relationship between of PAI-1 gene 4G/5G polymorphism and CAD, ACE gene I/D and AT1 gene A1166C polymorphisms are not related. PAI-1 gene homozygous genotypes may be considered as a prognostic marker for CAD patients.

Angiotensin-converting enzyme gene insertion/deletion polymorphism and hypertension disease.

Background: The renin-angiotensin system (RAS), which is important for controlling haemostasis in the body, can increase the development of essential hypertension (HTN). Various surveys have shown that ACE I/D polymorphism that influences ACE activity, a key component of RAS, has been known to be associated with the risk of HTN. The goal of this study was to investigate the correlation between ACE (I/D) polymorphism and HTN.Methods: Blood samples were obtained from 102 patients and 104 healthy individuals. The two groups were matched by age and sex. Informed consent was prepared for the study. The demographic data were collected using a questionnaire. White blood cells (WBCs) and then DNA were extracted from whole blood. After this, the PCR test was performed using specific primers. PCR products were examined using 1% agarose gel. Individuals with genotype II having a band of 490 bp, ID two band of 490 bp and 190 bp, and individuals with DD genotype, have a band in region 190 bp.Results: The average age of the patients was 52.7 ± 7.5 years. A significant difference was seen in the distribution of DD, II and I/D genotypes of ACE polymorphism between the essential hypertensive patients (44.1, 10.8, and 45.1%) and their ethnically matched healthy control (61.5, 3.8, and 24.6%, respectively). Our study showed an increased risk of disease in people with II genotype in comparison to ID and DD genotypes (0.46 (0.1-1.75) and 0.26 (0.05-0.94), respectively).Conclusions: The present study demonstrated that ACEI/D polymorphism is characterised with greater risk of essential HTN in the Lorestan province. II genotype increased the relative risk of essential HTN in the population. In the future, more investigations with more samples size are recommended for the better study of genetic factors in hypertensive patients.

Association between angiotensin-converting enzyme gene insertion deletion polymorphism and androgenetic alopecia susceptibility among Egyptian patients: A preliminary case-controlled study.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent condition with a complex etiopathogenesis. Angiotensin-converting enzyme (ACE) gene located on the chromosome 17q23 contains an insertion (I) and deletion (D) polymorphism in the intron 16. This gene polymorphism plays a role in multiple inflammatory disorders. However, there are no studies investigating its association with AGA susceptibility. OBJECTIVES: In this work, we aimed at exploring the association of ACE gene I/D polymorphism in AGA susceptibility in a group of Egyptian patients. METHODS: This study included 100 AGA patients, and 100 apparently healthy controls. The ACE gene I/D polymorphism was analyzed by polymerase chain reaction. RESULTS: The DD, ID genotypes, and D allele showed higher frequent distribution among studied AGA patients than controls (p < 0.05 each). Positive family history and ACE gene I/D polymorphism were considered AGA susceptibility predictors in both uni- and multivariable analyses [p < 0.05 each (OR (95% CI)] on applying logistic regression analysis for risk factors prediction. CONCLUSIONS: This study highlights the possible contribution of the suspected genetic polymorphism as a susceptibility indicator for AGA development in the examined group of patients.

Association Between Angiotensin-Converting Enzyme Gene I/D Polymorphism and Polycystic Ovary Syndrome Susceptibility: a Meta-analysis.

Rec ent studies have suggested a closer association between angiotensin-converting enzyme (ACE) gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results were inconsistent. We conducted this meta-analysis to explore the precise associations between ACE gene I/D polymorphism and PCOS risk. Online electronic databases (PubMed, Embase, SCI index, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between ACE gene I/D polymorphism and PCOS risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 12 published case-control studies with 2248 patients and 1759 controls were included according to the criteria. Significant increased risk was found for PCOS susceptibility with I/D mutation (D vs. I: OR = 1.62, 95%CI = 1.24-2.11, P < 0.01, I2 = 86.1%; DD vs. II: OR = 2.10, 95%CI = 1.35-3.27, P < 0.01, I2 = 79.8%; ID + DD vs. II: OR = 1.57, 95%CI = 1.06-2.32, P = 0.02, I2 = 79.3%; DD vs. II + ID: OR = 1.91, 95%CI = 1.39-2.65, P < 0.01, I2 = 79.1%). Furthermore, some similar associations were also observed in subgroups. In summary, the current evidences indicated that ACE gene I/D polymorphism plays an important role in PCOS development, both in Asian and Caucasian descendants.

The Determination Of The Relationship Between Vo2max And The Angiotensin-Converting Enzyme Gene (ACE) rs1799752 Polymorphisms In The Turkish National Ice Hockey Sports Team.

In the present study, the effect of ACE rs1799752 polymorphism on maximal oxygen consumption (VO2max) in ice hockey players was analyzed. For this reason, 21 male National Ice Hockey players, aged between 18-25, were recruited for the study. The conventional polymerase chain reaction (PCR) was used on the genotype rs1799752 polymorphism. The VO2max values were calculated by using the 20m Shuttle Run tests. The numbers and percentages of the II, ID and DD genotypes were 9 (%43), 7 (%33), and 5 (%24), respectively. The allelic distribution for I and D alleles was found to be 25 (60%) and 17 (40%), respectively. The mean VO2max of all the athletes was calculated as 47.52 ml. The mean VO2max of the II, ID, and DD genotypes were 49.74ml, 47.34 ml, and 46.43 ml, respectively. We found that the oxygen utilization capacity increased from the DD genotype to the II genotype. However, this increase was not statistically significant (p> 0.05). In order to confirm our findings, it is recommended that larger prospective studies depending on the effect of the relevant polymorphisms needed to be carried out.