Angiotensin-converting Enzyme Gene Polymorphism Research Articles

SUN-218 Evaluation of common polymorphisms of eNOS gene and ACE gene in ADPKD patients and their association with HTN and renal failure in ADPKD patients

Autosomal Dominant Polycystic kidney Disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) and generally a late-onset multisystem disorder characterized by: bilateral renal cysts; cysts in multiple cysts in other organs. Renal manifestations include hypertension, renal pain, and renal insufficiency. Risk factors for progressive CKD include: younger age at the diagnosis, large kidney volume (size) on imaging, rapid cyst growth, hypertension, male gender, visible hematuria, and inheritance of a PKD1 versus a PKD2 mutation. The role of Angiotensin Converting Enzyme (ACE) gene polymorphism and endothelial nitric oxide synthase (eNOS) gene polymorphism in the clinical course of ADPKD is not well understood and there is no available index to predict the outcomes and clinical course of ADPKD. Our study evaluated association between these polymorphisms and presence of hypertension and renal failure in ADPKD patients. In this case-control study, 75 ADPKD patients and 100 control wasparticipated. All cases were provided written informed consent 5 cc of whole blood was obtained and transferred to the EDTA solutionand whole bloods was preserved in the temperature of -70◦ c◦ . then all samples of whole blood was referred to the genetic laboratory and DNA was extracted from whole blood by the phenol chloroform extraction and ethanol precipitation techniques. Genotyping for I/D polymorphism in ACE gene and Glu 298 ASP and T 786C polymorphisms in eNOS gene was performed by ARMS- PCR and molecular,s evaluation by special primers for two set genes ; I/D polymorphism in ACE gene and Glu 298 ASP and T 786C polymorphisms in eNOS gene was performed . There were no significant difference between two groups in terms of age and sex. The frequency of DD polymorphism of ACE gene and TC polymorphism of T786C of eNOS were significantly higher in ADPK patients than control but there was no difference in term of Glu 298ASP polymorphisms of eNOS gene. In ADPKD patients, 29 patients (39%) had hypertension, 4 patients (5%) had diabetes, 43 patients (57%) had GFR less than 60mL/min/1.73m2, and 41 patients (55%) had creatinine more than 1.5 mg/mL. The polymorphisms of ACE and eNOS genes were not significantly different in terms of hypertension, diabetes, GFR and creatinine status in ADPKD patients (P>0.05). There was no association between ACE polymorphisms and eNOS gene polymorphisms with renal insufficiency and hypertension in ADPKD patients. It seems that more number of patients need for study on association between polymorphisms and manifestation of ADPKD.

ACE gene polymorphism and its association with serum erythropoietin and hemoglobin ‎in Iraqi hemodialysis patients.

PurposeTo evaluate the frequencies of angiotensin-converting enzyme gene ‎polymorphism in ‎Iraqi hemodialysis patients and to examine the association ‎between this polymorphism and ‎serum erythropoietin and hemoglobin levels.‎MethodsIn this study, 70 chronic renal failure Iraqi patients on ‎maintenance ‎hemodialysis (patient group) and 20 healthy subjects (control ‎group) were genotyped for ‎angiotensin-converting enzyme gene polymorphism. The distribution of genotype and allele ‎frequencies of this polymorphism in ‎these subjects were also evaluated.‎ResultsThe distribution of angiotensin-converting enzyme genotypes between ‎groups was ‎similar, and the ID genotype was the most frequent, followed by DD and II ‎genotypes (‎50%‎, ‎37%‎, and ‎13%). The control group ‎had a nonsignificant difference in serum ‎erythropoietin levels among different angiotensin-converting enzyme genotypes, ‎while patients with ID and DD genotypes displayed significant ‎elevation in ‎serum erythropoietin with time. No significant differences in hemoglobin ‎levels ‎were observed in patient and control groups. A significant positive correlation ‎was ‎observed between serum erythropoietin and hemoglobin in the control group ‎with different ‎angiotensin-converting enzyme genotypes, while a nonsignificant ‎negative correlation was ‎observed in the patient group throughout the study. ‎ConclusionsChronic kidney disease did not significantly alter angiotensin-converting enzyme ‎genotypes, and angiotensin-converting enzyme gene ‎polymorphism had a significant effect on ‎serum erythropoietin levels and a non‎significant effect on hemoglobin levels. ‎

Impact of angiotension I converting enzyme gene I/D polymorphism on running performance, lipid, and biochemical parameters in ultra-marathoners

The insertion (I) or deletion (D) polymorphism in the angiotension I converting enzyme gene, (ACE I/D, rs1799752) is associated with human exercise endurance and performance. However, most of the aforementioned studies focus on marathons, swimming, and triathlons, while the ACE polymorphism in ultra-marathoners has not yet been reported. We studied the impact of ACE I/D polymorphism in ultra-marathoners and investigated its relationship with lipid profiles, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) levels in runners before and after ultra-marathon racing.This observational study used data from a 100-km ultra-marathon in Taipei, Taiwan. Twenty-four male participants were analyzed for their ACE insertion/deletion polymorphism, lipid profiles, hs-CRP, IL-6 in serum immediately before and after ultra-marathon running.In our 24 subjects analyzed, 7, 14, and 3 subjects were of I/I, I/D, and D/D genotypes, respectively. Runners with the D polymorphism (I/D and D/D) showed a trend of better performance in the 100-km ultra-marathon (measured by completion time in minutes, P = .036). In this group, the previous best marathon performance was also significantly better than the I/I group (P = .047). After adjusting for body mass index (BMI), the difference in performance was not significant. Ketone levels, IL-6, and hs-CRP levels were highly increased at immediately and 24-hour post-race. No correlation was found between different ACE polymorphisms and common biochemical parameters examined.We report the first study in the impact of the ACE I/D (rs1799752) on ultra-marathoners. Presence of the D polymorphism in ACE gene is associated with better performance, although the BMI of the runners contribute as a major factor. There was no difference in the biochemical or lipid parameters measured among different ACE polymorphisms.

Association of ACE Gene Polymorphism with Hypertension and Metabolic Risk Factors among Indigenous People of the Northern Territory of Yakutia

Association of ACE Gene Polymorphism with Hypertension and Metabolic Risk Factors among Indigenous People of the Northern Territory of Yakutia

Deletion Polymorphism of Angiotensin Converting Enzyme Gene is Associated with Left Ventricular Hypertrophy in Uighur Hypertension-Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) Patients.

BackgroundThis study aimed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion polymorphisms with left ventricular hypertrophy (LVH) in Han and Uighur hypertension-OSAHS (obstructive sleep apnea hypopnea syndrome) patients in China.Material/MethodsA total of 162 Han and 72 Uygur patients with hypertension-OSAHS were independently subdivided into an LVH group and a non-LVH (NLVH) group based on the left ventricular mass index. The insertion/deletion polymorphisms of ACE gene were determined by polymerase chain reaction. The association of ACE gene insertion/deletion polymorphisms with LVH was assessed by chi-squared test. Logistic regression analysis was performed to obtain the odds ratios and 95% confidence intervals for the risk of LVH after adjusting for confounding factors.ResultsIn Uighur patients, the distributions of D allele and DD genotype showed significant differences between the LVH group and the NLVH group. The difference of DD genotype remained significant after multivariate adjustment. In contrast, no significant differences were observed in the distributions of D allele and DD genotype between the LVH group and the NLVH group in Han patients. Moreover, moderate-severe OSAHS was an independent risk factor for LVH.ConclusionsD allele and DD genotype of ACE gene are possible genetic markers for the risk of LVH in Uighur but not Han hypertension-OSAHS patients.

Cellular Aspects of Muscle Specialization Demonstrate Genotype - Phenotype Interaction Effects in Athletes.

IntroductionGene polymorphisms are associated with athletic phenotypes relying on maximal or continued power production and affect the specialization of skeletal muscle composition with endurance or strength training of untrained subjects. We tested whether prominent polymorphisms in genes for angiotensin converting enzyme (ACE), tenascin-C (TNC), and actinin-3 (ACTN3) are associated with the differentiation of cellular hallmarks of muscle metabolism and contraction in high level athletes.MethodsMuscle biopsies were collected from m. vastus lateralis of three distinct phenotypes; endurance athletes (n = 29), power athletes (n = 17), and untrained non-athletes (n = 63). Metabolism-, and contraction-related cellular parameters (such as capillary-to-fiber ratio, capillary length density, volume densities of mitochondria and intramyocellular lipid, fiber mean cross sectional area (MCSA) and volume densities of myofibrils) and the volume densities of sarcoplasma were analyzed by quantitative electron microscopy of the biopsies. Gene polymorphisms of ACE (I/D (insertion/deletion), rs1799752), TNC (A/T, rs2104772), and ACTN3 (C/T, rs1815739) were determined using high-resolution melting polymerase chain reaction (HRM-PCR). Genotype distribution was assessed using Chi2 tests. Genotype and phenotype effects were analyzed by univariate or multivariate analysis of variance and post hoc test of Fisher. P-values below 0.05 were considered statistically significant.ResultsThe athletes demonstrated the specialization of metabolism- and contraction-related cellular parameters. Differences in cellular parameters could be identified for genotypes rs1799752 and rs2104772, and localized post hoc when taking the interaction with the phenotype into account. Between endurance and power athletes these concerned effects on capillary length density for rs1799752 and rs2104772, fiber type distribution and volume densities of myofibrils (rs1799752), and MSCA (rs2104772). Endurance athletes carrying the I-allele of rs1799752 demonstrated 50%-higher volume densities of mitochondria and sarcoplasma, when power athletes that carried only the D-allele showed the highest fiber MCSAs and a lower percentage of slow type muscle fibers.DiscussionACE and tenascin-C gene polymorphisms are associated with differences in cellular aspects of muscle metabolism and contraction in specifically-trained high level athletes. Quantitative differences in muscle fiber type distribution and composition, and capillarization in knee extensor muscle explain, in part, identified associations of the insertion/deletion genotypes of ACE (rs1799752) with endurance- and power-type Sports.

Association among ACE, ESR1 polymorphisms and preeclampsia in Brazilian pregnant women

BackgroundGenetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. Material and MethodsThis case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. ResultsNo significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. ConclusionThis pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil.

The Effect of Angiotensin-Converting Enzyme Gene Polymorphisms on the Clinical Efficacy of Perindopril Prescribed for Acute Myocardial Infarction in Chinese Han Patients.

Objective: Perindopril is an angiotensin-converting enzyme (ACE) inhibitor that is commonly used in the treatment of Chinese Han patients with acute myocardial infarction (AMI). However, there have been few studies on whether polymorphisms of the ACE gene affect the efficacy of perindopril or the prognosis of AMI patients. The purpose of this study was to analyze the relationship among the ACE rs121912703 (C>T), rs767880620 (C>A), and rs397514689 (C>T) gene polymorphisms and the prognosis of AMI patients and the clinical efficacy of perindopril in the treatment of AMI. Methods: The ACE genotypes at the rs121912703, rs767880620, and rs397514689 loci in 225 AMI patients treated with perindopril were determined by polymerase chain reaction/Sanger sequencing. Differences in cardiac structure, functional indicators, hemodynamic parameters, and related laboratory indicators were detected before and after treatment. Results: After administration of perindopril, improved ventricular remodeling in AMI patients with wild-type ACE was better than in patients with the ACE rs121912703, rs767880620, and rs397514689 minor variant alleles. The patients harboring wild-type ACE had lower systolic blood pressure and diastolic blood pressure than the patients harboring the minor variant alleles (p < 0.01). The contents of serum ACE and Ang II (angiotensin II) in AMI patients carrying the wild-type ACE alleles were lower than those of patients harboring any of the minor variant alleles (p < 0.01). The 3-year survival time of AMI patients carrying the wild-type ACE alleles was markedly greater compared with AMI patients carrying the mutant genes (p < 0.01). Conclusion: Mutations at the ACE rs121912703, rs767880620, and rs397514689 loci affect the efficacy of perindopril on ventricular remodeling and hemodynamics in Chinese Han AMI patients. The 3-year survival of AMI patients harboring the variant alleles is less than that of the patients harboring the wild-type gene.

Association of Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism with the Risk of Atherosclerosis

Aims: The objective of this study was to perform a meta-analysis to evaluate the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and susceptibility to atherosclerosis (AS). Methods: MEDLINE, EMBASE, and the ISI Web of Science were searched for all eligible published studies concerning the relationship of ACE gene polymorphism with AS without language restrictions. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate this relationship under different genetic models using meta-analytic methods. Results: A total of 15 articles (16 studies) were involved in this meta-analysis. The D allele of the ACE gene had a nonsignificant increase in the risk of AS (D versus I: OR = 1.23, 95% CI, .98-1.53, P = .07; I2 = 87.2%, Pheterogeneity < .01). Compared with the II genotype, the DI (relative risk [RR]: 1.35, 95% CI: 1.09, 1.67, P < .01; I2 = 47.8%, Pheterogeneity = .017) and (DD + DI) (RR = 1.38, 95% CI: 1.04, 1.82, P = .02; I2 = 73.3%, Pheterogeneity < .01) genotype of ACE was associated with higher risk of AS, respectively. Subjects with the DD genotype showed a statistically nonsignificant trend toward greater risk of AS (RR = 1.53, 95% CI: .97, 2.43, P = .07; I2 = 88.6%, Pheterogeneity < .01). Further subgroup analyses showed that significant relationships were only found in Europeans under different gene polymorphism or different genotype models rather than Asians. Conclusions: The present meta-analysis indicated that the D allele in the ACE gene was associated with the risk of AS, especially in Europeans. Furthermore, increased copy number of D allele was significantly associated with increased AS risk in a dose-dependent manner.

Screening of Egyptian obese children and adolescents for insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme gene.

Background/aims: The role of angiotensin-converting enzyme (ACE) gene polymorphism in the development of obesity and hypertension in children has not been widely studied. We aimed to screen Egyptian obese children and adolescents for insertion/deletion (I/D) polymorphism in the ACE gene.MethodsOne hundred forty-two children and adolescents were included (70 with simple obesity and 72 controls). Blood pressure was measured, and anthropometric parameters were assessed in all included children and adolescents. Fasting lipid profile, fasting glucose, and insulin were measured. DNA extraction and ACE I/D polymorphism genotyping were also performed.ResultsObese children had a higher frequency of DD genotype (30% in obese versus 11.1% in controls, P = .01) and D alleles (61.8% in obese versus 48.6% in controls, P = .01). Obese children with hypertension and prehypertension had higher frequency of DD genotype than II genotype and higher D alleles than I alleles. DD genotype and D allele were independently associated with hypertension (OR: 9.86 and 11.57, respectively, P < .001), while dyslipidemia and insulin resistance were not associated with the ACE I/D gene polymorphism.ConclusionDD genotype and D-allele of the ACE gene polymorphism were associated with obesity and with hypertension and pre-hypertension in Egyptian children.

Effects of angiotensin converting enzyme gene polymorphism on hypertension in Africa: A meta-analysis and systematic review.

BackgroundHypertension is dramatically increasing in Africa with evidence of increased severity and resistance to treatment. Although angiotensin converting enzyme gene polymorphism is associated with higher prevalence of hypertension, the evidence is inconclusive on its influence on the emerging pattern in Africa. This meta-analysis is conducted to pool the available evidence to inform future research and interventions.MethodsArticles published through May 2018 were systematically searched in PubMed, Scopus and EMBASE databases. Studies were assessed for inclusion by two independent researchers. Six models were used to assess the effect of angiotensin converting enzyme deletion-insertion gene polymorphism. Heterogeneity and publication bias were tested and sensitivity analysis was carried out. Odds ratio and 95% confidence intervals were measured for pooled effect. Both random effect and fixed effect models were used, whilst the frequency of DD, II and DI genotypes were computed and compared.ResultPatients with D allele were 1.49 times more likely to develop essential hypertension compared with patients who carry the I allele (OR:1.49; CI:1.07, 2.07). Similarly, patients who had homozygous co-dominance genotype DD (i.e., DD vs II) were at a 2.17 times higher risk of essential hypertension compared to the co-dominant genotype II (OR:2.17, CI:1.79, 3.18), dominant model (I.e., DD+ID vs II) (OR:1.48; CI:1.03, 2.12), and recessive model (OR:1.64; CI:1.03, 2.61). On subgroup analysis, participants from Sub-Saharan Africa were more genetically susceptible to hypertension compared to their North Africa counterparts. There was no publication bias found, but there was high to moderate heterogeneity.ConclusionACE I/D polymorphism is associated with essential hypertension in Africa in the allele contrast model, as well as the dominant, recessive and homozygous codominance model. On subgroup analysis, ACE I/D was associated with essential hypertension in patients from Sub-Saharan Africa but not in North Africa. A future large scale study, which includes different ethnic groups, is recommended.

ACE Insertion/Deletion Polymorphism (rs4646994) Is Associated With the Increased Risk of Multiple Myeloma.

Introduction: The insertion (I allele) deletion (D allele) polymorphism of ACE gene (rs4646994) may influence the etiopathogenesis of multiple myeloma (MM). ACE gene is expressed in bone marrow cells and encodes angiotensin converting enzyme (ACE). It converts angiotensin I to active peptide angiotensin II, which stimulates proliferation of hematopoietic stem cells. This suggests possible association of ACE I/D gene polymorphism with MM. The aim of our study was to check possible impact of this polymorphism on risk of development and outcome of MM, as well as, sensitivity to bortezomib in cell cultures derived from MM patients.Objects and Methods: Genomic DNA from 98 newly diagnosed MM patients and 100 healthy blood donors were analyzed by PCR method. Chromosomal aberrations were detected by use of cIg-FISH. In a subgroup of 40 MM patients nucleated bone marrow cells were treated with bortezomib in vitro.Results: The Hardy-Weinberg equilibrium test showed that genotypic frequencies diverged significantly from the equilibrium. The differences between I and D allele frequencies in control and study population were significant (p = 0.046). We observed the association between DD genotype and more than 2-fold risk of MM - OR = 2.69; p < 0.0001. We did not detect any significant differences among studied genotypes regarding clinical and laboratory parameters. Moreover, we did not observe the association between survival of MM patients and I/D genotypes. Bortezomib increased number of apoptotic and necrotic cells, but the only statistically significant differences were observed in the number of viable cells at 1 nM between ID and DD genotypes (p = 0.026).Conclusion: Presented results confirmed the significant relationship between ACE (I/D) polymorphism and risk of MM development. We did not observe the association of ACE I/D polymorphism with disease outcome and bortezomib in vitro sensitivity.

Abstract WMP58: Sex Differences in Risk Factors for Aneurysmal Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis

Background: Aneurysmal subarachnoid hemorrhage (aSAH) disproportionally affects women. The etiology of this is unclear, and the contribution of sex differences in aSAH risk factors is unknown. We aimed to identify sex differences in aSAH risk factors in a systematic review and meta-analysis. Methods: A systematic search was conducted using the Pubmed, Scopus, Embase, and Medline databases from inception to November 2017 to identify studies that included aSAH risk factors stratified by sex. aSAH risk factors were assessed using meta-analysis with pooled odds ratios (OR) calculated for risk factors with at least 2 studies. Results: There were 34 eligible case-control studies; however, 15 did not report sex specific findings with 19 were included. Hypertension (men pooled OR adjusted 3.13 [95% CI 2.26-4.34]; women pooled OR adjusted 3.65 [95% CI 2.87-4.63], p=0.18), smoking (men pooled OR adjusted 2.96 [95% CI 1.68-5.21]; women pooled OR adjusted 3.11 [95% CI 1.21-7.97], p=0.95), family history of aSAH, increased systolic blood pressure, age, angiotensin-converting enzyme gene polymorphism and variation in a protease gene had the same odds for aSAH in both sexes. Alcohol intake (men pooled OR adjusted 1.50 [95% CI 1.04-2.17], women pooled OR adjusted 0.83 [95% CI 0.48-1.45], p=0.003), high alanine aminotransferase levels, and endothelial nitric oxide synthase gene variant were associated with higher odds of aSAH in men than women. Cold temperature, polymorphisms in factor XIII gene and genetic variation on chromosome 9p21 increased the odds of aSAH in women but not men. High aspartate aminotransferase levels were associated with a reduced risk in men while diabetes mellitus decreased the risk in women (men pooled OR adjusted 0.57 [95% CI 0.32-1.01], women pooled OR adjusted 0.24 [95% CI 0.13-0.43], p=0.017). Conclusion: Except for alcohol intake and diabetes mellitus, the magnitude of aSAH risk associated with most common risk factors were similar for both sexes. We advocate for re-analysis of existing studies with regard to sex differences.

Genetic Aspects of Preeclampsia: The Role of Polymorphisms in the Genes of the Renin-Angiotensin System.

Preeclampsia (PE) is a severe complication that develops in 10% pregnant women. It is the leading cause of maternal and perinatal morbidity and mortality worldwide. The goal of this study was to reveal the frequency of polymorphisms in the angiotensin-converting enzyme gene (ACE I/D) and type 1 angiotensin II receptor gene (AGTR1 A1166C) in pregnant women with severe early- and late-onset PE. A retrospective case-control study of 55 pregnant women with PE (main group) and 30 patients with uncomplicated pregnancy (control group) was conducted. In the main group, we considered two subgroups - early-onset PE (20 patients) and late-onset PE (36 patients). The I/D polymorphism of the ACE gene is associated with the risk of developing PE. The presence of the D allele increases the risk of severe PE. In case of DD genotype, the probability of early-onset PE is 5 times higher than that of the late-onset PE. The analyzed data confirm the involvement of renin-angiotensin system in the PE development. We conclude that the ACE gene polymorphism is a genetic predictor of the early-onset severe PE. Studying the polymorphic loci of the ACE gene makes it possible to use them for the individualized prognosis of the development and course of PE in patients.

ACE/ACTN3 GENETIC POLYMORPHISMS AND ATHLETIC PERFORMANCE OF FEMALE SOCCER PLAYERS`

ABSTRACT Objective: Previous studies have shown controversial relationships between ACE and ACTN3 gene polymorphisms and sports performance. Thus, the aim of our study was to assess anaerobic and aerobic performance indicators of young female soccer players with different ACE/ACTN3 gene profiles. Methods: Twenty-seven female soccer players aged 16-18 underwent acceleration, speed, strength, anaerobic power and aerobic endurance tests and had their ACE and ACTN3 polymorphisms determined. Results: Based on genetic analysis, they were divided into the following groups: ACE II (n=2), ACE ID (n=11), ACE DD (n=14), ACTN3 XX (n=5), ACTN3 RR (n=7) and ACTN3 RX (n=15). ACE DD and ACE ID groups differed significantly in terms of results achieved on the 5 m sprint test (1.15±0.05 s vs 1.10±0.05 s, P=0.42). ACTN3 RR and RX achieved better results than the ACTN3 XX group in seven continuous vertical jumps (26.57±1.59 cm vs 25.77±2.51 cm vs 22.86±1.16 cm, respectively; P=0.007 for RR vs XX and P=0.021 for RX vs XX). Conclusion: High prevalence of ACE DD and ACTN3 RX genotypes in our subjects may suggest that faster and more powerful young females tend to perform better in soccer. Nevertheless, the absence of differences in most of the physical test results indicates that different genotypes are compatible with high-level soccer performance, meaning that it is the phenotype-genotype interaction that makes a successful female soccer player. Level of Evidence I, Prognostic studies — Investigating the effect of a patient characteristic on disease outcome.

Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism Is Not Responsible for Antihypertensive Therapy Induced New Onset of Type 2 Diabetes in Essential Hypertension.

Background:Antihypertensive drug therapies have been reported to be associated with new onset of type 2 diabetes mellitus in some hypertensive patients after prolonged use. Angiotensin converting enzyme (ACE) gene has been found to affect essential hypertension, response of antihypertensive therapies, and glycemic disturbances. Therefore, ACE gene I/D polymorphism may be associated with risk of new onset of type 2 diabetes via metabolic disturbances, glycemic dysregulation, and insulin resistance.Aim:To assess the correlation between ACE gene I/D polymorphism and glycemic disturbance under influence of diuretic and other antihypertensive drug therapies.Materials and methods:We recruited 270 normotensive patients as control (150 men and 120 women), 270 hypertensive patients (95 men and 175 women), and 240 hypertensive with new onset of diabetes patients (80 men and 160 women). All samples were genotyped for ACE gene polymorphic alleles and relationship between different genotypes and anthropometric and clinical parameters along with drug therapies was established and analyzed.Results:Baseline clinical (systolic blood pressure, diastolic blood pressure, and fasting blood glucose level) and anthropometric parameters (height, weight, waist circumference, hip circumference, waist-hip ratio, and body mass index) of study populations were found highly statistically significant (P < .05) when compared among study groups. Furthermore, genotype wise comparison of all these parameters in essential hypertensive (EH) and essential hypertensive with onset of diabetes (EHNOD) patients found most of them nonsignificant and no variation was found with respect to different genotypes of ACE gene. The genotype wise comparison of clinical parameters among different antihypertensive drug therapy was found statistically nonsignificant in both EH and EHNOD patients.Discussion:Anthropometric parameters can be taken as the risk indicator factors for hypertension and diabetes. However, ACE gene polymorphism may not be a risk factor for development of diabetes in hypertensive patients.Conclusion:The present study suggested that ACE gene polymorphism did not show any significant association with the risk of new onset of diabetes in EH patients and more detailed studies with large population size are needed.

The Severity of Oxidative Stress in Comorbid Chronic Obstructive Pulmonary Disease (COPD) and Hypertension: Does it Depend On ACE and AGT Gene Polymorphisms?

There is an increasing number of studies suggesting the role of genetic factors in the development and progression of chronic obstructive pulmonary disease and hypertension. Therefore, our study aimed to establish the role of ACE and AGT gene polymorphisms in the mechanisms behind the development of oxidative stress in patients with concomitant chronic obstructive pulmonary disease and hypertension. The study group consisted of 96 patients: Group 1 (individuals with a chronic obstructive pulmonary disease), Group 2 (individuals with arterial hypertension), Group 3 (individuals with a chronic obstructive pulmonary disease and arterial hypertension). The control group consisted of 20 healthy subjects. ACE and AGT gene polymorphisms were determined by polymerase chain reaction amplification. Detection of intracellular reactive oxygen species levels was performed by EPICS XL cytometer (Beckman Coulter, USA) with dichlorodihydrofluorescein diacetate and dihydroethidium. Serum levels of 8-isoprostane were assayed with ELISA, Cayman Chemicals (USA). No significant correlations between ACE and AGT gene polymorphisms and parameters of oxidative stress in a setting of comorbid chronic obstructive pulmonary disease and hypertension were observed. However, the increase in oxidative stress parameters was observed to be the most significant in patients with chronic obstructive pulmonary disease + hypertension and with I/I genotype of the ACE gene, which was due to their lowest values in virtually healthy individuals. This suggests that I/I genotype may be associated with lower levels of reactive oxygen species production compared with other genotypes.

ACE gene Polymorphism on Diabetic Type 2 Patients and their Susceptibility to Diabetic Nephropathy

One of diabetic type 2 (T2D) complications is diabetic nephropathy, the glycated hemoglobin, poor diabetic control, are considered as risk factors for renal damage. current study aim the I/D polymorphism ACE gene and serum ACE levels may increase the diabetic nephropathy complications susceptibility in a sample population of Al-Najaf in Iraq. a total of 90 T2D patients(about 32 without nephropathy and 58 with nephropathy) and 50 healthy persons, all groups age were>45years old. The ACE I/D polymorphism was performed by polymerase chain reaction (PCR) using special primers, followed by electrophoresis on 1.5% agarose gel. we record significant differences between the ACE I/D polymorphism in T2D and control was (P < 0.01). the DD genotype of ACE I/D polymorphism the risk for T2D increased (OR=7.2 fold), as well as, the carriers D allele, the risk (OR=0.55). also T2D patients had a significantly higher level in ACE in diabetic nephropathy(DN) and lower level in T2D without nephropathy if compared with controls (P < 0.01). Our evident show the carriers DD genotype had more serum ACE levels than carriers II genotype in T2D.

Impact of Angiotensin-converting Enzyme and Matrix Metalloproteinase-3 Gene Polymorphisms on Risk for Developing Vascular Access Failure in Hemodialysis Patients - A Pilot Study.

For adequate hemodialysis, functional vascular access is obligatory. Neointimal hyperplasia (NIH) has a central role in stenosis and thrombosis development, which represent the most frequent causes of vascular access failure. Polymorphism of different genes that have a significant role in endothelial function may have an impact on NIH development. Therefore, the aim of our study is to determine the effect of angiotensin-converting enzyme (ACE) I/D and matrix metalloproteinase-3 (MMP3) 5A/6A polymorphism on risk for developing vascular access failure in hemodialysis patients. The study included 200 patients on regular hemodialysis at Nephrology Department, University Medical Center Zvezdara. Retrospective analysis included a collection of general and vascular access data from medical records. Genetic analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Patients were divided into two groups: Group 1—patients who have never experienced vascular access failure and Group 2—patients who have at least one spontaneous vascular access failure. There was no difference in age, gender, hemodialysis vintage, main diagnosis, presence of hypertension, and diabetes mellitus between the two groups. There were no statistically significant differences in the frequencies of ACE and MMP3 genotypes between the two groups. Without statistical significance, it was found that homozygotes for I allele had two times higher risk for developing vascular access failure than homozygotes for D allele (OR 2.00; 95%CI: 0.727–5.503; P = 0.180). In addition, patients with 5A allele have 1.7 times higher risk for developing vascular access failure compared with patients without this allele (OR 1.745; 95% CI: 0.868–3.507; P = 0.118). Patients with vascular access failure do not have different genotype distribution regarding ACE gene and MMP3 gene polymorphism as compared with patients without vascular access failure. Still, homozygotes for I allele and homozygotes for 5A allele have higher risk for developing vascular access failure compared with other patients.

Assessment of ACE A-240T Polymorphism with Chronic Kidney Disease in North Indian Population

Chronic kidney disease (CKD) is a major public health problem with high risk of morbidity and mortality. Angiotensin converting enzyme (ACE) gene plays a significant role in the pathogenesis of chronic kidney disease (CKD) in different ethnic groups. This study aimed to investigate an association between ACE (A-240T) gene polymorphism and CKD in North Indian population. This case-control study was conducted in 385 subjects- 165 patients with CKD and 220 healthy controls. Genotyping of ACE A-240T polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The AA genotype and the A allele distributions were higher in both groups than the TT genotype and the T-allele. But, the genotypic and allelic distributions were not statistically significant difference between CKD patients and healthy controls. Also, no significant difference was found between the two groups in dominant, recessive and codominant genetic models. Our study suggested that the ACE A-240T variant not seems to be a risk factor for CKD in North Indian population. Further studies with a larger sample size are needed to confirm these results.