Angiotensin-converting Enzyme Gene Polymorphism Research Articles

Angiotensin-converting enzyme insertion/deletion (I/D) gene polymorphism in Iraqi type 2 diabetic patients: association with the risk of cardiac autonomic neuropathy

BackgroundStudies have shown a direct association between angiotensin-converting enzyme (ACE) and diabetic neuropathies. As such, ACE gene polymorphisms could be a risk factor for cardiac autonomic neuropathy (CAN) in patients with diabetes. The objective of our study was to investigate the association of the ACE I/D gene polymorphism with the development of CAN in Iraqi patients with type 2 diabetes mellitus (T2DM).ResultsThis is a cross-sectional study that included 142 patients with T2DM comprising 62 males and 80 females, and 100 volunteers served as a healthy control group. Cardiac autonomic functions were tested using four standard Ewing’s noninvasive tests. Blood samples were taken for genetic evaluation of an ACE gene I/D polymorphism.Analyzing ACE gene polymorphism revealed that the D allele was far more frequent among patients with diabetes than healthy control subjects (76.07% vs. 62.67%). The frequency of I/I, I/D, and D/D genotypes in patients with diabetes was 8.55%, 30.77%, and 60.68%, respectively, compared with 18.67%, 37.33%, and 44%, respectively, in controls with a significant difference in mutant homozygous genotype. However, there were no significant differences in these genotypes between patients with and without CAN. Although patients with CAN showed a much higher frequency of D allele than those without CAN, the difference did not reach significance (p = 0.054).ConclusionThe DD genotype and D allele of the ACE I/D gene polymorphism can be a risk factor for T2DM, and the D allele of this polymorphism can even be associated with the development of CAN in these patients.

Associations of Angiotensin-Converting Enzyme Gene Insertion/Deletion (ACE Gene I/D) Polymorphism With Vitiligo: An Updated Systematic Review and Meta-Analysis.

ObjectiveThe objective of the article is to summarize the current evidence regarding the association between angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism and vitiligo disease.MethodsA computerized search was performed through four electronic databases (PubMed, Scopus, Cochrane Central Register of Controlled Trials [CENTRAL], and Web of Science) with the relevant keywords. Included studies comprised of papers examining the association of ACE gene polymorphisms with vitiligo. Data were pooled as an odds ratio (OR) in random- and fixed-effect models using the Mantel-Haenszel (M-H) method. Review Manager 5.3 software (clicktime.com, Inc., San Francisco, US) was utilized in the meta-analysis. ResultsTen studies (n=2,740) matching the inclusion criteria were included in the systematic review and meta-analysis. Results showed no significant difference between individuals carrying deletion/deletion (D/D) genotype and individuals with deletion/insertion (D/I) + insertion/insertion (I/I) genotypes in terms of vitiligo risk (odds ratio [OR]=1.13, 95% confidence interval [CI]: 0.78 to 1.64, p=0.53). However, vitiligo risk was higher in the individuals carrying the I/D genotype when compared with individuals with D/D + I/I genotypes (OR=1.29, 95% CI: 1.10 to 1.52, p=0.001). Moreover, the increased risk was observed in individuals carrying D/D when compared with I/I (OR=1.67, 95% CI: 1.33 to 2.09, p<0.0001). D allele was associated with significant risk when compared with the I allele (OR=1.29, 95% CI: 1.15 to 1.45, p<0.0001).ConclusionThe current evidence suggests that there is a significant association between ACE I/D gene polymorphism and vitiligo. These findings support the use of ACE polymorphism in the prediction of vitiligo as a biomarker.

Angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism in Egyptian children with congenital heart disease.

Congenital heart diseases (CHDs) are the leading cause of infant deaths worldwide. The relationship between angiotensin-converting enzyme (ACE) gene polymorphism and CHDs is not clear. The aim of this work is to assess the presence of an association between ACE I/D polymorphism and CHD in Egyptian population. Seventy CHD cases and 70 controls were incorporated in this study. DNA was isolated from their peripheral blood, and then ACE I/D gene polymorphism was tested by polymerase chain reaction (PCR). There was no significant difference among the frequencies of the DD, II, and DI genotypes in patients and controls (26 [37.1%], 37 [53.3%], and 4 [5.7%], 5 [6.7%]), 40 (57.2%), 28 (40%), respectively (p value = 1 and OR [95% CI] = 1.1). There was no significant difference between D allele (DD + DI) and II genotype distribution among patients and controls (p value = 1 and OR [95% CI] = 1.2 [0.3-2.9]). Moreover, there was no difference between I allele (II + DI) and DD frequency (p value = 0.2 and OR [95% CI] = 0.6 [0.3-1.2]). ACE I/D gene polymorphism might not be a risk factor of CHD in Egyptian children. Additional widespread studies are needed to affirm these data.

Role of genetic factors in the development of hypertension in young patients with metabolic syndrome

Results of the study related to polymorphism of ACE gene (rs1799752)‎, integrin αIIbβ3, and CSK gene (rs1378942) influencing development of arterial hypertension in young patients with metabolic syndrome are presented. Hypertension as a component of the metabolic syndrome was detected in 15.0% of young patients. Prevalence of mutant alleles of the studied genes among the examined patients was quite high, so homozygous DD genotype was found in 21.6%, and mutant D allele of the ACE gene in 47.4%. A high risk of hypertension in patients with MS was detected in carriers of the T allele of the CSK (rs1378942) gene – 54.8%, which was most often observed in a combination of polymorphic ACE and CSK gene loci (p = 0.0053).

Genetics and the Elite Athlete: Our Understanding in 2020.

Modern competitive sport has evolved so much that athletes would go to great extremes to develop themselves into champions; medicine has also evolved to the point that many genetic elements have been identified to be associated with specific athletic traits, and genetic alterations are also possible. The current review examines the published literature and looks at three important factors: genetic polymorphism influencing sporting ability, gene doping and genetic tendency to injury. The ACTN3 gene has an influence on type II muscle fibres, with the R allele being advantageous to power sports like sprinting and the XX genotype being associated with lower muscle strength and sprinting ability. The ACE gene polymorphisms are associated with cardio-respiratory efficiency and could influence endurance athletes. Many other genes are being looked at, with specific focus on those that are potentially related to enhancement of athletic ability. Recognition of these specific gene polymorphisms brings into play the concept of genetic engineering in athletes, which constitutes gene doping and is outlawed. This has the potential to develop into the next big threat in elite sports; gene doping could have dangerous and even fatal outcomes, as the knowledge of gene therapy is still in its infancy. Genetic predisposition to injury is also being identified; recent publications have increased the awareness of gene polymorphisms predisposing to injuries of ligaments and tendons due to influence on collagen structure and extracellular matrix. Ongoing work is looking at identifying the same genes from different races and different sexes to see if there are quantitative racial or sexual differences. All of the above have led to serious ethical concerns; in the twenty-first century some sports associations and some countries are looking at genetic testing for their players. Unfortunately, the science is still developing, and the experience of its application is limited worldwide. Nevertheless, this field has caught the imagination of both the public and the sportsperson, and hence the concerned doctors should be aware of the potential problems and current issues involved in understanding genetic traits and polymorphisms, genetic testing and genetic engineering.

Renin-angiotensin aldosterone profile before and after angiotensin-converting enzyme-inhibitor administration in dogs with angiotensin-converting enzyme gene polymorphism.

BackgroundAn angiotensin‐converting enzyme (ACE) gene polymorphism occurs in dogs; however, functional importance is not well studied.HypothesisWe hypothesized that dogs with the polymorphism would show alternative renin‐angiotensin aldosterone system (RAAS) pathway activation and classical RAAS pathway suppression before and after ACE‐inhibitor administration, as compared to dogs without the polymorphism that would show this pattern only after ACE‐inhibitor administration.AnimalsTwenty‐one dogs with mitral valve disease that were genotyped for the ACE gene polymorphism.MethodsThis retrospective study utilized stored samples from 8 ACE gene polymorphism‐negative (PN) dogs and 13 ACE gene polymorphism‐positive (PP) dogs before and after enalapril administration. Equilibrium analysis was performed to evaluate serum RAAS metabolites and enzyme activities. Results were compared before and after enalapril, and between groups.ResultsThe classical RAAS pathway was suppressed and the alternative RAAS pathway was enhanced for both genotypes after administration of enalapril, with no differences before enalapril administration. Aldosterone breakthrough occurred in both PN (38%) and PP (54%) dogs despite angiotensin II suppression. Aldosterone was significantly higher (P = .02) in ACE gene PP dogs (median, 92.17 pM; IQR, 21.85‐184.70) compared to ACE gene PN dogs (median, 15.91 pM; IQR, <15.00‐33.92) after enalapril.Conclusions and Clinical ImportanceThe ACE gene polymorphism did not alter baseline RAAS activity. Aldosterone breatkthrough in some dogs suggests nonangiotensin mediated aldosterone production that might be negatively influenced by genotype. These results support the use of aldosterone receptor antagonists with ACE‐inhibitors when RAAS inhibition is indicated for dogs, especially those positive for the ACE gene polymorphism.

Correlation of ACE Gene Polymorphism and Hypertension in Stroke Ischemic Patients

Stroke is the third highest cerebrovascular disease in the world with high mortality and disability rate that is mostly dominated by ischemic stroke. Genetic factor that had been reported to have an indirect effect in increasing the incidence of ischemic stroke is ACE gene polymorphism. ACE gene polymorphism is characterized by the insertion marked by letter (I) or deletion marked by letter (D) on intron 16, chromosome 17. ACE gene polymorphism has drawn a lot of attention from scientists and had been reported to have an indirect effect in increasing the ischemic stroke incidence through pathogenesis of hypertension and atherosclerosis. In this study, 78 subjects of ischemic stroke consist of 43 subjects with hypertension and 35 subjects with normotension. I allele of ACE gene polymorphism was more dominant than D allele in hypertensive ischemic stroke patients (72.1% &gt; 27,9%) and this dominance was also seen in the incidence of hypertension vs normotension (55.4% &gt; 44.6%). However, the correlation of ACE gene polymorphism with the incidence of hypertension was not statistically significant when compared based on its genotype (p=0.280) and allele (p=0.948).

Meta-analysis of the relationship between the polymorphism of ACE and TNF-α gene and the susceptibility of sarcoidosis

Objective To evaluate the relationship between angiotensin converting enzyme (ACE) and tumor necrosis factors-α (TNF-α) gene polymorphism and sarcoidosis. Methods Meta analysis was carried out by retrieving the studies published up to July 2018 to evaluate the relationship between ACE and TNF-α gene polymorphism and sarcoidosis. RevMan 5.3 and Stata 12.0 software were used to analyze the combined OR value and 95% confidence interval (95% CI) by recessive model and dominant model. The stability of the results was judged by ethnic subgroup analysis and sensitivity analysis. Results A total of 28 articles and 30 studies met the inclusion criteria, including 7 888 cases, 2 992 cases of sarcoidosis and 4 896 healthy controls. No significant association was found between ACE I/D and sarcoidosis using any model (P>0.05). TNF-α-308A/G was significantly associated with sarcoidosis risk (OR=1.34, 95% CI=1.13-1.58, P=0.0007). Ethnic subgroup analysis showed that the results were significantly different in both the Caucasians (OR=1.36, 95% CI=1.13-1.64, P=0.001) and the Asians (OR=4.88, 95% CI=1.43-16.99, P=0.01). Conclusions The meta-analysis identified that AA/AG genotypes at TNF-α-308 were associated with susceptibility to sarcoidosis .However, no significant correlation was found between ACE I/D and the susceptibility of sarcoidosis. Key words: Tumor necrosis factor-alpha; Angiotensin-converting enzyme; Gene polymorphism; Sarcoidosis; Meta-analysis

Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children

Bronchial asthma (BA) has a polygenic nature, and the onset of its manifestation and features course is realized due to the influence of genetic factors. This study aimed to investigate the effect of polymorphisms of the genes of the phase II detoxification system and genes of the cardiovascular tone on the severity of asthma in children. The study included 163 children aged 5–18 years: 38 with severe asthma, 69 with moderate asthma, and 56 with mild asthma. A molecular genetic study was conducted to determine the frequency of gene propagation and gen-gene interaction by GSTT1, GSTM1, GSTP1, ACE, eNOS, AT2R1, NAT2 genes at different severity of bronchial asthma. Found that in the prediction of the severity of asthma special place belongs to the analysis of the combination of genotypes. Independent effects were found for AT2R1 and ACE gene polymorphisms. The ACE (I / D) / AT2R1 (A1166C) / eNOS (T786C) / eNOS (4b / 4a) four-locus model was developed to predict the severe BA course and the need for additional analysis of the interaction of AT2R1 (A1166C) and eNOS (T786C), eNOS (T786C) genes was demonstrated (4b4a) and GSTT1. The risk of developing severe BA has been demonstrated for the combination of 1166SS + 786TT, 1166CC + 786TC genotypes by AT2R1 (A1166C) and eNOS (T786C) genes, and the reduction of this risk for combinations of eNOS (4b4a) 4b4b + GSTT1 genotypes. In moderate asthma, combinations of ACE genotypes DD + AT2R1 1166SS and AT2R1 313AA + GSTP1 1166SS were reliable risk markers for severe asthma. AT2R1 gene polymorphism was the leading marker in more severe asthma. A marker of severe BA was also found for the heterozygous 857GA polymorphism of the NAT2 gene (G857A). Conclusions. The influence of ACE (I / D), AT2R1 (A1166C), eNOS (T-786C), NAT2 (G857A), GSTT1, and GSTP1 gene polymorphisms on the severity of asthma in children has been established.

DD genotype of the I/D Angiotensin-Converting Enzyme Gene Polymorphism is a higher Risk for Atopic Asthma

Background: Atopic asthma begins with exposure to allergens causing airway hyperresponsiveness and chronic inflammation. Angiotensin II involved in the pathogenesis of atopic asthma by causing airway hyperresponsiveness. Angiotensin II levels are influenced by the levels of ACE and ACE levels are influenced by I / D ACE gene polymorphisms. Study about the role of I/D ACE gene polymorphism in the incidence and severity of asthma in several countries and etnic showed inconsistency result. Study in Indonesian subjects had never been reported. Method: This Case-control study aimed to evaluate influence of I/D ACE gene polymorphism in incidence and severity of atopic asthma. Eighty subjects aged 15-50 years including Forty non–asthmatic and Forty atopic asthmatic patients were included in this study.. Result: DD genotype with atopic asthma (85.7%) was higher than non atopic asthma (14,3%). Non-DD genotype (ID,II) with atopic asthma (46.6%) was lower than atopic asthma (53.4%). DD genotype of the ACE gene had risk 6.8 times to become atopic asthma than non-DD genotype (OR=6.8,p=0.05). DD genotype of ACE gene was not a risk factor for severe obstruction (OR=0.50, p=0.48) and uncontrolled atopic asthma compared to non-DD genotype (OR = 1.8,p=0.49) Conclusions: This study concluded that DD genotype of ACE gene was a risk factor for the incidence of atopic asthma but not a risk factor for severe obstruction and uncontrolled atopic asthma.

Assessment of insertion/deletion polymorphism of ACE gene as a genetic risk marker for preeclampsia in pregnant women.

To investigate the possible associations of angiotensin converting enzyme insertion or deletion genotypes and alleles with the risk of preeclampsia in Arab women. The case-control study was conducted from January 2016 to December 2017 at King Abdulaziz University Hospital and Maternity & Children Hospital, Jeddah, Saudi Arabia, and comprised pregnant women withpreeclampsia as cases and normal pregnant women as controls. Deoxyribonucleic acid was extracted and angiotensin-converting enzyme gene was amplified by polymerase chain reaction analysis and characterised through gel electrophoresis. Of the 162 women, 68(42%) were cases and 94(58%) controls. The mean values of age, body mass index, and systolic and diastolic blood pressure were significantly different among the cases than the controls (p<0.05), but mean gestational age did not significantly differ between the groups (p>0.05). The distribution of the polymorphic variants of the angiotensin converting enz yme gene insertion/deletion was not significantly different between the groups (p>0.05). Also, genotype distribution and allelic frequencies were not significantly different between the groups (p>0.05). For insertion/deletion polymorphism, no significant differences were detected in the genotype and allele frequencies or any of the inheritance models between preeclampsia patients and controls.

Pharmacogenetic study of ACE, AGT, CYP11B1, CYP11B2 and eNOS gene variants in hypertensive patients from Faisalabad, Pakistan.

To investigate the association of genetic variants of renin angiotensin aldosterone system, endothelial nitric oxide synthase and 11-beta-hydroxylase genes, and the drug efficacy of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. This two time-point study was conducted from April to November 2016 at Allied Hospital, Faisalabad and National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, and comprised of hypertensive patients taking angiotensin-converting enzyme inhibitor and angiotensin receptor blocker who were followed up for 12 weeks. Baseline and follow-up clinical and biochemical parameters were measured for all patients. Total 11 polymorphisms were genotyped by polymerase chain reaction, polymerase chain reaction-restriction fragment length polymorphism and amplification-refractory mutation system-polymerase chain reaction assays. Data was divided into baseline and follow-up groups, while the latter group was further divided into responding and non-responding subgroups on the basis of patient response to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker drugs. Data was analysed using SPSS 20. Of the 45 patients, 25(55.5%) were females and 20(44.5%) were males. There was a significant reduction in the systolic blood pressure (p=0.004) and low-density lipoprotein cholesterol (p<0.001) from the baseline to the follow-up. Systolic blood pressure was significantly reduced in the responding group (p=0.003), while diastolic blood pressure (p=0.121) was not significantly different. There was no effect of angiotensin-converting enzyme, angiotensinogen, 11-beta-hydroxylase, aldosterone synthase and endothelial nitric oxide synthase gene polymorphisms on angiotensin converting enzyme inhibitor and angiotensin receptor blocker efficacy. Inter-individual response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker was found to be independent of genetic polymorphisms in renin angiotensin aldosterone system, endothelial nitric oxide synthase and 11-beta-hydroxylase genes.

ACE gene I/D polymorphism and arterial hypertension in patients with COPD

Abstract Background Cardiovascular diseases (CVDs) are common in people with chronic obstructive pulmonary disease (COPD), and their presence is associated with an increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality. We assessed the role of angiotensin-converting enzyme (ACE) gene polymorphism in the occurrence of arterial hypertension (AH) in patients with COPD. Methods The study group consisted of 96 patients. Group 1 had 25 individuals with COPD, Group 2 had 23 individuals with AH and Group 3 had 28 individuals with COPD and AH. The control group consisted of 20 healthy subjects. I/D genotypes of ACE were determined by polymerase chain reaction amplification. Results The frequency distribution of polymorphic genotypes of the gene encoding ACE and assessment of compliance with the Hardy-Weinberg population equilibrium were carried out in groups of patients with COPD, AH and COPD + AH combination. The frequencies of the genotype responsible for I/D polymorphism of the ACE gene in the control and experimental groups were not found to deviate significantly from the Hardy–Weinberg equilibrium. The results of the study have not demonstrated any significant impact of alleles of ACE genes or ACE genes on occurrence of diseases such as COPD, AH and combinations thereof. However, analysis of odds ratio has demonstrated that the presence of the D allele of the ACE gene may increase the risk for occurrence of the COPD + AH (OR = 1.26). Conclusion The data obtained in the study allow suggesting that the presence of D allele of the ACE gene may increase the risk for AH in patients with COPD.

Evaluation of common polymorphisms of eNOS gene and ACE gene in autosomal dominant polycystic kidney disease patients and their association with hypertension and renal failure

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most hereditary renal disease that leads to end-stage renal disease (ESRD). Objectives: Since there is no available parameter to assess the clinical course of ADPKD and its outcome, yet, the aim of our study was evaluation of the association of common polymorphisms of eNOS and ACE genes with clinical manifestations (kidney failure and hypertension) in ADPKD. Patients and Methods: Seventy-five ADPKD patients and 100 control subjects participated in our study. Around 7.5 cc of whole blood was taken from each participant and sent to the genetic laboratory. DNA was obtained from them by the phenol chloroform extraction and ethanol precipitation techniques. Then genotyping for I/D polymorphism of ACE gene and Glu298 ASP and T786C polymorphisms of eNOS gene was performed by PCR electrophoresis and molecular evaluation by special primers for two genes. Results: The frequency of DD polymorphism of ACE gene and TC polymorphism of T786C of eNOS were considerably elevated in ADPKD individuals than control subjects. No significant difference between groups regarding Glu298 ASP polymorphisms of eNOS gene was detected. In ADPKD patients, 29 patients (39%) had hypertension, 5 patients (6.7%) had diabetes and 43 patients (57%) had glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 . The polymorphisms of ACE and eNOS genes were not meaningfully different regarding diabetes, high blood pressure, GFR and plasma creatinine in ADPKD individuals (P&gt;0.05). Conclusion: In our study, we could not find any association between polymorphisms of ACE and eNOS genes with renal insufficiency and hypertension in ADPKD patients.

Update on the genotyping distribution, epidemiology and associated risk factors in inflammatory disorder in adult subjects: A cross-sectional study

Limited molecular studies have been documented with ACE gene polymorphism in OA and RA in the major industrial city in the country. The current study aims to investigate the prevalence of the arthritis risks and perform the ACE gene polymorphism in OA and RA in hospital based population. In this hospital-based study, we adopted 1000 arthritis subjects; 539 was suffering with OA and 461 RA in the local hospital. Based on the filled questionnaire and signed consent form, patients were involved in this study. Genotyping was performed in 1000 arthritis subjects. Our results indicated the risk of BMI and smoking status in both OA and RA diseases. Most of the participants involved in this study were considered to opt the non-vegetarian rather than the vegetarian. The arthritis patients were interested in eating the chicken (65.7%) and then red meat (31.5%). Regular walking (22.4%) was found to be higher in the arthritis patients than the regular exercise (4.7%). However, males are more active than the females in both the regular exercise and regular walking. Most of the arthritis patients (37.3%) had the comfortable sleep duration between 9 and 10 h. The prevalence of arthritis has been increased and patients with high BMI should be growing the risks of the various arthritis. Simultaneously, weight gain is connected with both the OA and RA diseases. Physical activity is required to reduce the risks of arthritis. The present study recommends to avoid the smoking and maintain the normal BMI specifically in the females to avoid the arthritis disease in Faisalabad city in the Pakistan.

INFLUENCE OF GENE POLYMORPHISM OF THE RENIN-ANGIOTENSIN SYSTEM ON THE COURSE OF EARLY BACTERIAL INFECTIONS IN PREMATURE INFANTS

In the perinatal-specific infection mortality pattern, bacterial sepsis of newborns and congenital pneumonia account for 23.5% and occupy the I rank. Among the many non-specific clinical signs of infection, hemodynamic disorders are dominant in the development of adverse medical effects. Polymorphism of genes of the renin-angiotensin system, as one of the regulating units, can lead to peculiarities of disorders of hemodynamics in the infectious process.&#x0D; Aim of the study: to study the effect of ACE, AGT2R1 and eNOS gene polymorphism on the development of early bacterial infections and their most severe manifestation – arterial hypotension syndrome.&#x0D; Materials and Methods: two groups of children were formed to achieve the goal. The main group includes 121 prematurely born infants with bacterial infections of the early neonatal period, and the comparison group includes 31 prematurely born infants with no signs of early bacterial infections. Genetic methods included the study of ID polymorphism of ACE gene, AC polymorphism of gene AGT2R1 gene polymorphism and 4a/4b polymorphism of eNOS.&#x0D; Analysis of vital functions in children stratified according to the genotype of the ACE gene, showed that at the first day of life in prematurely born children with genotype II, the mean blood pressure was significantly higher than in children with the genotype ID (35.3 ± 1.55 mm Hg) and 31.7 ± 0.88 mmHg, respectively, p = 0.033). In children with the II genotype of ACE, the hourly diuresis rate at day 1 was significantly lower than in children with the DD genotype (1.6 ± 0.2 ml/kg/h and 2.2 ± 0.21 ml/kg/h, respectively, p = 0.0017), which may indicate better renal circulation in children with the DD genotype. As a result of the study, no influence of the genes of the renin-angiotensin system on the fact of early bacterial infections occurrence was found, but significant influence of the CC-genotype of the AGT2R1 gene on the development of arterial hypotension syndrome in premature infants (OR = 10.17) was detected.&#x0D; A practical recommendation for public health may be to conduct a genetic study to identify ACE and AGT2R1 gene polymorphisms in preterm infants, which will help identify the risk group for systemic and organ haemodynamic disorders and manage it individually.

Association between ACE gene polymorphism and carotid stenosisand and construction of related gene regulatory networks.

ObjectiveTo investigate the association between DD, ID and II genotypes of ACE gene and carotid stenosis, and to construct a network of ACE-related genes regulating carotid stenosis.ApproachesMeta-analysis was used to study the association between three genotypes DD, ID and II of carotid stenosis susceptibility gene ACE; functional annotation of ACE gene was conducted by GO analysis; and a network of ACE-related genes that regulate the mechanisms of carotid stenosis was established.ResultsMeta-analysis showed that DD and II genotypes of ACE gene were associated with carotid stenosis. GO analysis showed that the main biological processes involved in ACE include: the process of transforming angiotensinogen into mature angiotensin; angiotensin’s mediation of the brain's response to alcohol consumption and thirst control; any chemical reaction involving the regulation of angiotensin; and the process of catalyzing the release of a C-terminal dipeptide from a polypeptide chain. A network of ACE gene regulation of carotid stenosis was constructed in combination with KEGG analysis.ConclusionThe ACE gene is a susceptibility gene for carotid stenosis. Through the functional annotation and pathway analysis of ACE gene, an ACE gene-involved carotid stenosis regulatory mechanisms network was constructed.

The Association of ACE Gene polymorphism and Some Biomarkers in Hemodialysis Patients

The Aim: Chronic kidney disease (CKD) is clarified by constant structural abnormalities, urine abnormalities or damaged excretory renal function indicative of a failure of functional nephrons. One of the treatments for renal fail¬ure is hemodialysis. The aim was assessing the potential association between Angiotensin Converting Enzyme (ACE) gene I/D polymorphism with renal failure and their correlation with some biochemical parameter as Insulin-like Growth Factor 1 (IGF-1) and Symmetric Dimethyl Arginine (SDMA) and kidney function test "urea" and "creatinine" in Iraqi hemodialysis patients. Materials and Methods: The study was contained 60 hemodialysis patients (30 Male and 30 Female).The control group was 30 healthy subjects (15 Male and 15 Female). The ages of hemodialysis patients and control groups ranged between (11-75 years). The information was taken from a questionnaire which included age, sex, smoking, duration of disease, duration of dialysis, number of dialyses, other disease and family history. Also, BMI, urea, creatinine, IGF-1, and SDMA were measured. After extraction of DNA from white blood cells and carrying out of PCR, characterizing ACE I/D polymorphism by applying an amplification refractory mutation system (ARMS) technique. Results: The demographic study showed that there were more hemodialysis patients had age ≥ 50 years old (40%)when compared with the control group. The most hemodialysis patients had body mass index (BMI) were 18-24.9 (48.33%)in comparison with control group which was18-24.9 (100 %). The smoking percentage was (16,67%) in hemodialysis patients compared to control group (10%). The presence of another disease in the hemodialysis patients were hypertension (70 %) followed by diabetes mellitus (25 %), arthritis (23.33%), and cardiovascular disease (20 %). With respect to family history of CKD, (25%) of hemodialysis patients have a family history while the family history of the control group was (6.67%). In the hemodialysis patients, the genotype I/I, I/D, and D/D distribution percentage were 18.33 %, 65 %, and 16.67% respectively compared with the control group which was 33.33 %, 36.67%, and 30 % respectively. Conclusion: There was a high association between heterozygous genotype (I/D) with the occurrence of CKD. Serum urea level increased in hemodialysis patients had ID genotypes in comparison with II and DD genotypes. Also, of IGF-1 and SADMA has importance as a risk factor or prognosis indicator in adult CKD hemodialysis patients.

The combination of ACE I/D and ACE2 G8790A polymorphisms revels susceptibility to hypertension: A genetic association study in Brazilian patients.

BackgroundSystemic arterial hypertension (SAH) is a multifactorial condition that already affects one third of the worldwide population. The identification of candidate genes for hypertension is a challenge for the next years. Nevertheless, the small contribution of each individual genetic factor to the disease brings the necessity of evaluate genes in an integrative manner and taking into consideration the physiological interaction of functions. Angiotensin I–converting enzymes, ACE and ACE2, are key regulators of blood pressure that have counterbalance roles by acting on vasoactive peptides from Renin-Angiotensin-Aldosterone System (RAAS). Insertion/deletion (I/D) polymorphism of ACE gene and single nucleotide polymorphism G8790A of ACE2 gene have been associated with susceptibility to SAH, but the literature is controversial. We proposed to evaluate these two polymorphisms jointly exploring the combined effects of ACE and ACE2 genotypes on SAH susceptibility, an approach that have not been done yet for ACE and ACE2 polymorphisms.Methods and findingsThis genetic association study included 117 hypertensive (mean age 59.7 years) patients and 123 normotensive and diabetes-free controls (mean age 57.5 years). ACE and ACE2 polymorphisms were genotyped by SYBR Green real-time PCR and RFLP-PCR, respectively. Crude and adjusted odds ratio (OR) values were calculated to estimate the susceptibility to SAH development. It was obtained homogeneity regarding distribution by sex, age range, smoking, alcohol consumption and body mass index (BMI) between case and control groups. No-association was verified for each gene individually, but the combination of ACE and ACE2 polymorphisms on female gender revealed a significative association for DD/G_ carriers who had a 3-fold increased risk to SAH development (p = 0.03), with a stronger susceptibility on DD/GG carriers (7-fold increased risk, p = 0.01). The D allele of ACE showed association with altered levels of lipid profile variables on case group (VLDL-cholesterol, p = 0.01) and DD genotype in all individuals analysis (triglycerides, p = 0.01 and VLDL-cholesterol, p = 0.01).ConclusionThese findings indicate that the combination of ACE and ACE2 polymorphisms effects may play a role in SAH predisposition been the DD/G_ genotype the susceptibility profile. This result allowed us to raise the hypothesis that an increased activity of ACE (prohypertensive effects) in conjunction with reduced ACE2 activity (antihypertensive effects) could be the underlining mechanism. The association of ACE D allele with lipid alterations indicate that this can be a marker of poor prognostic on SAH evolution and contribute to CVD development. Although these preliminary findings must be confirmed by further researches with larger sample size, we could observe that the integrative analysis of ACE and ACE2 can be an informative tool in hypertension understanding that needs to be explored in new studies.

Evaluation of the possible association of body mass index and four metabolic gene polymorphisms with longevity in an Italian cohort: a role for APOE, eNOS and FTO gene polymorphisms

Background: Longevity is considered the result of interactions between environmental and genetic factors.Aim: To investigate the possible association of body mass index and the frequencies of APOE, ACE, eNOS and FTO gene polymorphisms with longevity.Subjects and methods: In total, 1100 healthy volunteers aged 10–100 were recruited. Subjects were genotyped for APOE, ACE, eNOS and FTO gene polymorphisms. Data about height and weight were also collected. The sample was split into four age groups: 1–24, 25–49, 50–85 and 86–100 years.Results: Significant differences were found in BMI values between age groups. A significant decrease of the APOE4, eNOS 393 and FTO A and allele frequencies was observed in the 86–100 age group compared to the younger groups. For ACE gene, no significant differences were found in the allele frequencies between groups. A similar trend was also observed when the sample was subdivided into two main age groups: 1–85 and 86–100 years.Conclusion: This study provides evidence for a role of APOE, eNOS and FTO gene polymorphisms in longevity. It has been estimated that the number of centenarians worldwide will double each decade until 2100, making population data about gene polymorphisms relevant for further studies about longevity.