Angiotensin-converting Enzyme Gene Polymorphism Research Articles

Assessment of angiotensin converting enzyme gene polymorphism in patients with psoriasis

Psoriatic patients had diversity of clinical presentations and complications. Psoriasis can have significant interference with the patient's quality of life, recovery, and outcome. Some evidences suggest that the angiotensin converting enzyme (ACE) is present in the skin of psoriatic patients. This study intended to assess the patterns of ACE insertion/deletion (ACE ID) polymorphism and the levels of serum ACE among psoriatic patients in comparison to normal controls. The study included two groups: 20 patients with psoriasis and 20 apparently healthy adults with negative family history of psoriasis as a control group. Psoriasis area and severity index (PASI) was used to measure of severity of psoriasis. In both groups, ACE ID gene polymorphism was assessed by quantitative real-time polymerase reaction and serum ACE levels was evaluated using an enzyme-linked immunosorbent assay. ACE ID genotype was significantly higher among the psoriatic group in comparison to the control group (40.0% versus 15.0%, respectively, p=0.016). D allele was significantly higher among the psoriatic group than the control group (25.0% versus 7.5%, respectively, p=0.034). ACE ID genotype carried significantly higher risk in psoriatic group versus control group (OR=3.8). The D allele carried higher risk in psoriatic group versus control group (OR=4.1). ACE serum levels were significantly higher among the psoriatic group compared to the control group (87.4±7.03 versus 2.3±0.7, respectively; p < 0.001). We concluded that ACE ID gene polymorphism may be considered as a risk factor for developing psoriasis.

Study of angiotensin-converting enzyme insertion/deletion polymorphism in Egyptians with Chronic Kidney Diseases: A case-control study

Kidney disease is clinically characterized by increasing rates of urinary albumin excretion, starting from normo-albuminuria, which progresses to microalbuminuria, macro albuminuria nephropathy, and eventually to end stage renal disease. This study aimed to estimate the frequencies of different polymorphisms of ACE gene in chronic kidney disease, and Healthy control. A case-control study design was carried out on 207 patients they were classified into 104 nephrotic syndrome and 103 chronic kidney injury patients in addition to 102 healthy subjects. The I/D polymorphism of the ACE gene was determined sequences of the sense and antisense primers PCR was performed in a final volume of 50 μl. Results: Genotype frequencies 2nd PCR (II, ID and DD-genotypes) in control group were found to be 12, 74 and 58; respectively while genotype frequencies 2nd PCR (II, ID and DD-genotypes) in CKD group were 0, 45 and 58; respectively. In Chronic Kidney Disease (CKD) patients, there were significant increase in [Creatinine (mg/dL), Cholesterol (mg/dL), T.G (mg/dL), LDL (mg/dL), Uric Acid (mg/dL)], 7.70 ± 2.98, 236.45 ± 42.19, 256.41 ± 43.11, 149.78 ± 12.78, 6.68 ± 0.82; respectively compared to control group (p&lt;0.01). But there was a significant decrease in albumin 3.02 ± 0.419, compared to control group (p&lt;0.01). From this study we conclude that there is a correlation between polymorphism of angiotensin converting enzyme gene and chronic kidney disease, especially DD genotype, which increases the chances of development to the stage of renal failure.

Association of gene polymorphisms of ACE, AGT, and ARNT-like protein 1 with susceptibility to gestational diabetes

Background and aimsGestational diabetes mellitus is well-defined as glucose intolerance first documented during pregnancy. In this study, we examined the possible associations between I/D polymorphism of the angiotensin-converting enzyme gene, the M235T variant of angiotensinogen gene, and the rs7950226 polymorphism of the ARNT-like protein-1 (BMAL1) gene and the risk for diabetes in Egyptian pregnant women.Subjects and methodsThis study recruited 160 gestational diabetes cases and 165 controls. Genomic DNA was derived from peripheral blood leukocytes and ACE gene (I/D) genotyping was performed using the method of polymerase chain reaction and the polymerase chain reaction-based restriction fragment length polymorphism was used for identifying the M235T variant of AGT gene and the rs7950226 polymorphism of the BMAL1.ResultsThe II, ID, and DD genotypes of the ACE gene have significant differences in cases compared to controls (P = 0.000 and X2 = 81.77). The M235T polymorphism of the AGT gene was increased with gestational diabetes risk. Furthermore, the AA genotype of the BMAL1 rs7950226 gene was significantly related to the gestational diabetes risk (P = 0.000 and X2 = 52.82). Furthermore, the allele frequencies of the three variants have significant variances between cases and control.ConclusionThis study suggested significant associations between ACE (DD), AGT (TT), and BMAL1 rs7950226 (AA) gene polymorphisms with gestational diabetes susceptibility and there was a possibility to identify that II + MM + GG as protective haplotypes and DD + TT + AA as risk haplotypes for gestational diabetes.

Polymorphisms in Exon 13 of Angiotensin-Converting Enzyme Gene among Hypertensive Patients in Sudan

Background: The identification of the critical regions within angiotensin-converting enzyme (ACE) gene which predict hypertension and/or influence ACE activity would have significant implications for precision medicine. Studies investigating the association of ACE gene polymorphisms and the risk of developing hypertension have yielded inconsistent results. Objective: The aim of the study is to identify single nucleotide polymorphisms (SNPs) or haplotype markers in exon 13 of ACE gene and their association with essential hypertension in a sample of Sudanese population. Methods: Amplified fragments of 550bp across exon 13 of ACE gene were outsourced to the Macrogen Company, Seoul, South Korea for sequencing. Finch TV program was used to view the chromatogram. Gene sequences were translated into amino acid sequence, using GeneMark version 4.25. The structural effect of a point mutation in a protein sequence was analyzed using PROJECT HOPE online website. Linkage disequilibrium between polymorphic variants was determined using Haploview v4.2. Results: Seven polymorphisms of ACE gene were identified in the sequenced fragments: four exonic SNPs (Rs4316, rs4317, rs4318 and one unreported SNP); an intronic SNP (rs12720723); one SNP at the intronic-exonic boundary site (rs4320); and an intronic I/D (rs4319). Haplotype analysis identified two blocks within 550bp spanning area of the ACE gene. Both blocks were composed of six SNPs: rs12720723; unreported SNP; rs4316; rs4317; rs4318 and rs4319. Each block consisted of five haplotype structures. Block 1 included B1-H1 (GCC), B1-H2 (ACC), B1-H3 (GCT), B1-H4 (GAT) and B1-H5 (AAT), whereas block 2 included B2-H1 (TAC), B2-H2 (CGC), B2-H3 (TAA), B2-H4 (CAC) and B2-H5 (TGC). Rs4317 and rs4318 were in moderate linkage disequilibrium (LD) (D’ value=0.69) among hypertensive patients. Rs4316; rs4319 and rs4320 were in moderate to high LD and displayed relatively high MAF among hypertensive participants. Conclusion: The results of our study suggest that the 3 SNPs within exon 13 of the ACE gene (rs4316, rs4319 and rs4320) could be genetic markers for developing hypertension as evidenced by the high LD and MAF observed in hypertensive participants. Moreover, rs4318 being in LD with rs4317 could highlight the importance of block 2 in predicting hypertension among blacks.

Relationship between Polymorphism of Angiotensin Converting Enzyme Gene with Symptoms of Depression in Schizophrenic Patients

In schizophrenic patients, symptoms of depression are often found which can lead to adverse effects on the treatment process, such as increasing the length of treatment, increasing the possibility of relapse, non-adherence in taking medication, and can also lead to suicide in schizophrenic patients. In schizophrenic patients, the activity of the central angiotensin converting enzyme (ACE) gene is altered and angiotensin II interacts with central dopamine, thereby contributing to the pathophysiology of schizophrenia. In addition, it is likely that the ACE gene variant is also involved in the development of depressive symptoms in schizophrenic patients. This research is a categorical analytic study with a cross sectional method, the sampling method is non-probability sampling with consecutive sampling type, with a total sample of 42 people. There was no significant difference between depression symptoms and ACE gene polymorphisms with P value = 0.746. There was no significant difference between depression symptoms and ACE gene polymorphisms.

Association of Angiotensin-Converting Enzyme Inhibitor Gen PolyMorphism with Electrocardiography and Echocardiography Findings in Hemodialysis Patients

Background: Gene polymorphism of angiotensin-converting enzyme (ACE) may be associated with adverse prognosis and increased cardiovascular complications in hemodialysis patients. Objectives: This study aimed to compare the frequency of ACE gene polymorphism in both hemodialysis patients and normal individuals considering echocardiographic findings. Methods: This cross-sectional study included 110 hemodialysis patients (case) and 113 healthy subjects (control). Gene polymorphism of ACE was evaluated in both groups. ECG and echocardiography tests were performed for all patients. Correlations between gene polymorphisms and other variables were analyzed in this study. Polymerase chain reaction (PCR) was used to identify the short deletion allele (D with 190bp), large insertion allele (I with 490bp), and ID genotype which has both alleles. Results: Case and control groups included 46 and 54 female and 64 and 59 male patients, respectively. There were no significant differences between the prevalence of DD, II, and DI alleles of the ACE gene with DI as the most common allele in both groups. No significant differences were found between systolic and diastolic blood pressure and heart rate in DD, DI, and II alleles of the case group. Echocardiographic findings of the patients showed no significant differences between DD, DI, and II genotypes of the case group and intraventricular septal end-diastole (IVSd), MVE vel, MVA vel, MVE/A ratio, MV DT, and MV Dec slope. The mean±SD left ventricular end-diastolic diameter (LVEDD) in II, ID, and DD patients were 4.3±0.72, 4.52±0.66, and 4.89±0.93 respectively (P=0.046). Conclusion: The findings of the present study showed that there were no differences in the prevalence of alleles of an ACE gene in hemodialysis patients and control groups. Moreover, no significant associations were observed between alleles of an ACE gene in the patients' group and echocardiographic findings except in left ventricular end-diastolic diameter.

Evaluation of insertion/deletion (I/D) polymorphisms of ACE gene and circulating levels of angiotensin II in congenital anomalies of the kidney and urinary tract.

Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) are defined as a heterogeneous group of anomalies that resulted from defects in kidney and urinary tract embryogenesis. CAKUT have a complex etiology. Genetic, epigenetic and environmental factors have been investigated in this context. Angiotensin II is a potent vasoconstrictor and exerts an important role in kidney embryogenesis. The angiotensin-converting enzyme (ACE) converts Angiotensin I into Angiotensin II (Ang II) and ACE gene has insertion/deletion (I/D) polymorphisms that have been evaluated in several nephropathies. This study aimed to evaluate whether the I/D polymorphisms of ACE gene and the circulating levels of Ang II are associated with any CAKUT phenotype or CAKUT in general. Our study was performed with 225 pediatric patients diagnosed with CAKUT and 210 age-and-sex matched healthy controls. ACE I/D alleles were analysed by real-time polymerase chain reaction (RT-PCR). The distribution of ACE I/D polymorphisms were compared between CAKUT patients and healthy controls, as well between ureteropelvic junction obstruction (UPJO), vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK) phenotypes and control group. No statistical association was detected between ACE I/D polymorphism and CAKUT and UPJO, VUR, and MCDK phenotypes. In a subset of 80 CAKUT patients and 80 controls, plasma levels of Ang II were measured. No significant differences were found between CAKUT patients and controls, even in regard to comparisons of UPJO, VUR and MCDK with control group. Although CAKUT is a complex disease and the ACE gene may exert a role in kidney embryogenesis, CAKUT was not associated with any ACE I/D polymorphisms nor with differences in plasma levels of Ang II in this Brazilian pediatric population.

Study of association of ACE gene I/D polymorphism with the risk of pulmonary sarcoidosis (with the participation of the Republic of Karelia residents)

The aim of the study was to analyze the association of I/D polymorphism of angiotensin-converting enzyme (ACE) gene with the risk of pulmonary sarcoidosis in ethnic Russians of the Republic of Karelia. Methods. The study enrolled 242 individuals, including 112 patients of Russian nationality residing in the Republic of Karelia with confirmed pulmonary sarcoidosis and 130 healthy donors as a control group. The distribution of alleles and genotypes of I/D polymorphism of ACE gene (rs4646994) in these groups was investigated. Alleles of this polymorphic marker were identified by the method of PCR-RFLP. Results. The comparative analysis showed no statistically significant differences in the distribution of alleles and genotypes of indel locus of ACE gene (rs4646994) between the control group and the group of patients with pulmonary sarcoidosis (χ2 = 0.619; p &gt; 0.05; χ2 = 0.368; p &gt; 0.05, respectively). Conclusion. I/D polymorphism of ACE gene is not associated with the risk of pulmonary sarcoidosis in ethnic Russians of the Republic of Karelia

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.

Are angiotensin converting enzyme (ACE1/ACE2) gene variants associated with the clinical severity of COVID-19 pneumonia? A single-center cohort study.

The impact of the coronavirus disease 2019 (COVID-19) pandemic has been unceasingly ongoing worldwide. Recent bioinformatics analysis and epidemiologic studies have highlighted that the functional polymorphisms on the angiotensin converting enzyme (ACE) gene may have an impact on the clinical progress of COVID-19. In this study, we aimed to determine the impact of the ACE1 gene I/D polymorphism and ACE2 peptidase-2 domain variants on disease severity. Hundred patients with confirmed COVID-19 related pneumonia [50 patients with severe disease in intensive care unit (ICU) and 50 patients not in ICU] were compared on the basis of genetic and clinical characteristics. Genomic DNA was purified from peripheral blood lymphocytes with an automated QIA symphony DSP DNA Mini-Kit. The Sanger sequencing analysis was performed. The frequencies of ACE1 gene polymorphism and ACE2 PD variants were compared in patients hospitalized in ICU and those not in ICU. The Statistical Package for Social Sciences version 22.0 was used for statistical analysis. The sequencing analysis of the ACE2 gene exon 1 and 2 revealed none of the polymorphisms investigated or any other variants in the present cohort. The frequencies of the ACE1 ID, DD, and II genotypes were 51%, 31%, and 18%, respectively. The frequency of the D allele was similar between the ICU and non-ICU groups (50.4% versus 49.6%). Older age and the presence of advanced stage radiologic abnormalities on admission were detected as independent predictors of ICU requirement. No effect of any ACE1 gene polymorphism on predicting ICU requirement was detected. To the best of our knowledge, this is the first study investigating the impact of ACE gene polymorphisms on clinical severity of COVID-19 in a Turkish cohort.

Дослідження зв’язку поліморфізмів генів ACE, AGT та FGB із ризиком раннього розвитку ішемічного інсульту атеротромботичного підтипу в популяції осіб, які проживають на території України

Актуальність. Атеротромботичний підтип ішемічного інсульту становить 50 % випадків захворювання та є причиною інвалідизації працездатного населення середнього віку. Судинні порушення можуть бути пов’язані зі змінами у структурі генів ангіотензинперетворюючого ферменту (АСЕ), ангіотензиногену (AGT) та бета-фібриногену (FGB). Мета дослідження. Дослідити зв’язок наявності I/D (rs1799752) поліморфізму гена АСЕ, Т174М (rs4762) поліморфізму гена AGT та С-148Т (rs1800787) поліморфізму гена FGB із ризиком раннього розвитку ішемічного інсульту атеротромботичного підтипу в популяції осіб білої раси, які проживають на території України. Матеріали та методи. Генетичний аналіз було проведено 78 хворим (24 жінки, 54 чоловіки), які перенесли ішемічний інсульт, та 55 особам популяційного контролю (20 жінок, 35 чоловіків), які не мали тяжких серцево-судинних захворювань. Середній вік пацієнтів експериментальної групи становив 53,9 ± 9,43 року, групи контролю — 59,8 ± 14,8 року. Поліморфізми генів AGT та FGB досліджували методом полімеразної ланцюгової реакції з подальшою рестрикцією ампліфікованих фрагментів. Генотипування поліморфізму I/D гена АСЕ було проведено методом алель-специфічної полімеразної ланцюгової реакції. Результати. Дослідження ризику розвитку захворювання показало, що носії I/D- та DD-генотипу гена АСЕ мають менший ризик захворіти на ішемічний інсульт атеротромботичного підтипу, ніж носії I/І-генотипу (OR = 0,303, 95% CI 0,134–0,688; р &lt; 0,05, та OR = 0,303, 95% CI 0,134–0,688; р &lt; 0,05 відповідно). Носії поліморфного генотипу -148СТ гена FGB частіше ніж удвічі ризикують захворіти на ішемічний інсульт (OR = 2,452; 95% CI 1,201–5,005; р &lt; 0,05), ніж носії генотипу -148СС. Зв’язок поліморфізму гена AGT T174M із ризиком розвитку ішемічного інсульту був відсутній. Висновки. Поліморфний генотип -148С/Т гена FGB, а також алель І та генотип ІІ гена АСЕ є факторами ризику раннього розвитку ішемічного інсульту атеротромботичного підтипу в популяції осіб, які проживають на території України.

Effect of angiotensin converting enzyme gene polymorphism on patients with in-stent restenosis after percutaneous coronary intervention

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To evaluate the association between common single nucleotide polymorphisms (SNPs) in angiotensin converting enzyme (ACE) gene and the risk of in-stent restenosis (ISR) and/or the response to angiotensin converting enzyme inhibitor ACEI in individuals with stable coronary artery disease (CAD) after stent implantation.&#x0D; Methods: The total population of this study consisted of 200 Egyptian individuals divided into 2 groups - in-stent restenosis (ISR) and non ISR group). Genomic DNA was withdrawn from EDTA whole blood applying a spin column approach and ACE gene insertion/deletion (I/D) polymorphisms were determined by polymerase chain reaction (PCR).&#x0D; Results: Carriers of allele D of ACE gene were significantly more liable to ISR occurrence. However, carriers of allele I were significantly more liable to ISR occurrence after administration of ACEI. There is a negative interaction between DD genotype of ACE gene and ACEI administration on ISR after percutaneous coronary intervention (PCI). However, there is a positive interaction between II and ID genotype of ACE gene and ACEI administration on ISR after PCI with bare metal stents (BMS).&#x0D; Conclusion: It is beneficial to implement ACEI in therapeutic regimen in individuals with ID or II genotypes of ACE gene, especially with BMS implementation.&#x0D; &#x0D; &#x0D; &#x0D;

Association of angiotensin converting enzyme gene polymorphism with survival of extremely low birth weight infants

<h3>ЦЕЛЬ ИССЛЕДОВАНИЯ</h3> Оценить связь выживаемости детей с экстремально низкой массой тела, нуждающихся в проведении искусственной вентиляции легких и в инотропной поддержке, с полиморфизмом гена ангиотензинпревращающего фермента (<i>ACE</i> (Ins-Del). <h3>МАТЕРИАЛ И МЕТОДЫ</h3> Дизайн исследования<b></b> — контролируемое, проспективное, нерандомизированное, одноцентровое. Критерии включения — новорожденные с экстремально низкой массой тела, гестационный возраст менее 29 недель, искусственная вентиляция легких более 3 суток. Критерии невключения — множественные пороки развития, врожденный порок сердца, гестационный возраст менее 25 недель. В работу включено 88 пациентов с массой тела от 990 до 770 г. Конечная точка — уровень летальности, умерло 12 детей. Основную группу составили 35 пациентов, которым проводилась инотропная поддержка добутамином более 24 ч, группу сравнения — 53 новорожденных с кратковременной инотропной поддержкой добутамином. <h3>РЕЗУЛЬТАТЫ</h3> Статистически значимые межгрупповые различия по частоте выявления генотипов и аллелей гена <i>ACE</i> нами не получены, как не выявлены и преимущества в выживаемости исследуемых недоношенных младенцев с экстремально низкой массой тела, не являющихся носителями мутантной аллели D гена <i>ACE</i> (c²=0,553, <i>p</i>=0,458). <h3>ЗАКЛЮЧЕНИЕ</h3> Носительство мутантной аллели<b></b> гена ангиотензинпревращающего фермента (<i>ACE</i>(Ins-Del)<i></i> не ассоциировано с выживаемостью новорожденных с экстремально низкой массой тела, нуждающихся в проведении искусственной вентиляции легких и инотропной поддержке.

Correlation of Angiotensin-converting Enzyme 2 Gene (rs1514283) Polymorphism with the Incidence of COVID-19.

It has been a busy year for coronaviruses, with the most recent one causing severe coronavirus illness in 2019 (COVID-19). It is broadly distributed in many human tissues and organs as the potential SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2). ACE2 provides homeostatic modulation of circulation angiotensin II levels by acting as a physiological counterbalance to ACE. They have been linked to COVID-19 disease acquisition, progression, and severity. As a result, we investigated how ACE2 variations and epigenetic variables affect SARS-CoV-2 infection susceptibility and infection outcomes in terms of age, gender, and ethnicity. Debates raged over the etiology of this occurrence. It is important to note that further research is required to demonstrate the efficacy of human recombinant ACE2 and ACE2-derived peptides in fighting SARSCoV-2 variants. Better recognition of a host genetic, as well as the function of the properties of ACE2 variations, would assist in explaining clinical disparities of infection between individuals and contribute to the development of remedies and managing future SARS-CoV-2 epidemics, an essential function for ACE2 in essential hypertension (EH). We wanted to see how ACE2 gene polymorphisms and enzyme activity correlated with COVID-19 incidence in the Iraqi province of Al-Diwaniya. A total of 63 COVID-19 patients and 70 (NT) controls were genotyped using Sequenom Mass-ARRAY RS1000 for ACE2. Participants' ACE2 rs1514283 SNP was linked to COVID-19.

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

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. 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. 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). 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.

Early Evidence on Genetic Polymorphisms in Conferring A "Two-Hit" Propensity to Renal Injury in Asian Indian Children.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of end-stage renal disease in children. While certain nephrogenic genes have been incriminated in these malformations, data to identify the frequency of gene polymorphisms in Asian Indian children with CAKUT are scarce. This study was done to identify the effect of polymorphisms in paired-box gene 2 (PAX2), bone morphogenetic protein (BMP)-4, angiotensin-converting enzyme (ACE), and angiotensin II receptor Type 2 (AGTR2) nephrogenic genes on the development of CAKUT. In this prospective cohort study, 158 children <12 years old (86 cases with CAKUT and 72 age-matched controls) were analyzed. DNA from both sets was extracted from peripheral blood using the Keygen DNA extraction kit, and single-nucleotide gene polymorphisms (SNPs) in PAX2, BMP-4, ACE, and AGTR2 nephrogenic genes were detected by polymerase chain reaction (PCR) using previously published primers and PCR conditions. The presence of A allele SNP for AGTR2 gene at rs3736556 was found to be significantly correlated with the development of ureteropelvic junction obstruction and vesicoureteral reflux (VUR) with the TT allelic genotype having a lower incidence of pelviureteric junction obstruction (odds ratio [OR] 0.18 [95% confidence interval [CI], 0.06-0.55], P = 0.01) and VUR (OR 0.31 [95% CI, 0.11-0.91], P = 0.03). Furthermore, on substratification of the patients with the presence of the A allele of AGTR2, 24 out of 27 patients with scarring were found to harbor the D allele of the ACE gene, thus predisposing them to further renal damage. This study points to early evidence in the implication of nephrogenic genes in development as well as predisposition to renal injury in Asian Indian patients with CAKUT.

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.

The Impact ofACEandACE2Gene Polymorphisms in Pulmonary Diseases Including COVID-19

Chronic and acute respiratory diseases pose a major problem for public health worldwide due to the high morbidity and mortality rates, while treatment options remain mostly symptomatic. The renin-angiotensin system (RAS) plays an important role in lung tissue, regulating pulmonary circulation and blood pressure, but also contributing to normal pulmonary function and development. Angiotensin-converting enzyme (ACE) and its homologous angiotensin-converting enzyme 2 (ACE2) are considered to be amongst the main RAS regulators and are highly expressed in the pulmonary vascular endothelium. This review discusses the impact of ACE and ACE2 functional gene polymorphisms on seven major pulmonary diseases, in terms of predisposition, course, and outcome, revealing their potential utility as both genetic markers and biomarkers. The discussed conditions include chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), asthma, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), lung cancer and pulmonary sarcoidosis (PS), as well as SARS-CoV-2 viral infection and COVID-19 disease.

Effect of rs4646994 polymorphism of angiotensin-converting enzyme on the risk of nonischemic cardiomyopathy.

Background: Angiotensin-converting enzyme (ACE) gene polymorphisms have recently been shown to be associated with risk of developing left ventricular hypertrophy (LVH). However, the results were controversial. We aimed to conduct this meta-analysis to further confirm the association between ACE rs4646994 polymorphism and hypertrophic cardiomyopathy (HCM)/dilated cardiomyopathy (DCM).Methods: PubMed, Embase, the Chinese National Knowledge Information, and Wanfang databases were searched for eligible studies. The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of included studies. Then we evaluated the association between ACE gene mutation and HCM/DCM by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs). Subgroup analysis was further performed to explore situations in specialized subjects. Sensitivity analysis and publication bias was assessed to confirm the study reliability.Results: There were 13 studies on DCM (2004 cases and 1376 controls) and 16 studies on HCM (2161 controls and 1192 patients). ACE rs4646994 polymorphism was significantly associated with DCM in all genetic models. However, in HCM, four genetic models (allele model, homozygous model, heterozygous model, and dominant model) showed significant association between ACE rs4646994 polymorphism and DCM. In subgroup analysis, we found that ACE rs4646994 polymorphism was significantly associated with DCM/HCM in Asian population. Finally, we also conducted a cumulative meta-analysis, which indicates that the results of our meta-analysis are highly reliable.Conclusion: ACE rs4646994 polymorphism increases the risk of DCM/HCM in Asians, but not in Caucasians. More case–control studies are needed to strengthen our conclusions and to assess the gene–gene and gene–environment interactions between ACE rs4646994 polymorphism and DCM/HCM.

Angiotensin-converting enzyme polymorphisms AND Alzheimer's disease susceptibility: An updated meta-analysis.

Many studies among different ethnic populations suggested that angiotensin converting enzyme (ACE) gene polymorphisms were associated with susceptibility to Alzheimer's disease (AD). However, the results remained inconclusive. In the present meta-analysis, we aimed to clarify the effect of ACE polymorphisms on AD risk using all available relevant data. Systemic literature searches were performed using PubMed, Embase, Alzgene and China National Knowledge Infrastructure (CNKI). Relevant data were abstracted according to predefined criteria. Totally, 82 independent cohorts from 65 studies were included, focusing on five candidate polymorphisms. For rs1799752 polymorphism, in overall analyses, the insertion (I) allele conferred increased risk to AD compared to the deletion (D) allele (I vs. D: OR = 1.091, 95% CI = 1.007-1.181, p = 0.032); while the I carriers showed increased AD susceptibility compared with the D homozygotes (II + ID vs. DD: OR = 1.131, 95% CI = 1.008-1.270, p = 0.036). However, none of the positive results passed FDR adjustment. In subgroup analysis restricted to late-onset individuals, the associations between rs1799752 polymorphism and AD risk were identified using allelic comparison (OR = 1.154, 95% CI = 1.028-1.295, p = 0.015, FDR = 0.020), homozygotes comparison, dominant model and recessive model (II vs. ID + DD: OR = 1.272, 95% CI = 1.120-1.444, p < 0.001, FDR < 0.001). Nevertheless, no significant association could be revealed after excluding studies not in accordance with Hardy-Weinberg equilibrium (HWE). In North Europeans, but not in East Asians, the I allele demonstrated increased AD susceptibility compared to the D allele (OR = 1.096, 95% CI = 1.021-1.178, p = 0.012, FDR = 0.039). After excluding HWE-deviated cohorts, significant associations were also revealed under homozygotes comparison, additive model (ID vs. DD: OR = 1.266, 95% CI = 1.045-1.534, p = 0.016, FDR = 0.024) and dominant model (II + ID vs. DD: OR = 1.197, 95% CI = 1.062-1.350, p = 0.003, FDR = 0.018) in North Europeans. With regard to rs1800764 polymorphism, significant associations were identified particularly in subgroup of European descent under allelic comparison (T vs. C: OR = 1.063, 95% CI = 1.008-1.120, p = 0.023, FDR = 0.046), additive model and dominant model (TT + TC vs. CC: OR = 1.116, 95% CI = 1.018-1.222, p = 0.019, FDR = 0.046). But after excluding studies not satisfying HWE, all these associations disappeared. No significant associations were detected for rs4343, rs4291 and rs4309 polymorphisms in any genetic model. Our results suggested the significant but modest associations between rs1799752 polymorphism and risk to AD in North Europeans. While rs4343, rs4291 and rs4309 polymorphisms are unlikely to be major factors in AD development in our research.