Angiotensin-converting Enzyme DD Research Articles

PREDICTORS OF MAXIMUM STEP LENGTH IN OLDER ADULTS: ROLES FOR STRENGTH AND ACE GENOTYPE

Abstract Deficits in step length, assessed clinically by the maximum step length (MSL) test, are associated with poor balance and falls, in older adults. Determining predictors of MSL would facilitate targeted interventions to improve balance and reduce falls in older adults. Angiotensin-converting enzyme (ACE) insertion/deletion polymorphism genotypes interact with strength to predict stepping speed, but the interplay between ACE genotype, strength and MSL is unclear. Our objective was to determine whether strength and ACE DD genotype, through main effects or interactively, are associated with MSL, in older adults. Adults (N=103, female=58.2%, mean age 72.1 years, range 65-85 years) provided demographic, health and balance confidence information, completed grip strength and MSL testing, and provided saliva for genotyping. Multiple regression determined variance in MSL explained by strength, DD genotype (present/absent), and strength x genotype interaction, while controlling for covariates (age, sex, self-rated health and balance confidence). Covariates (model 1) explained 47.7% of MSL variance, while adding grip strength (model 2) explained additional 9.7% of variance. Adding DD genotype (model 3) explained .2%, while adding a strength x genotype interaction term (model 4) explained additional 3.4%, of MSL variance. The final model explained 61% of the variance in MSL (p<.001). DD genotype did not independently predict MSL (β=-.053; p=.421), but was interactively with strength, a significant predictor (β=.216; p=.005) of MSL. Strength was a significant predictor (β=.264; p=.003) of MSL, and as a modifiable physiological factor should be a focus of rehabilitation interventions to improve MSL and reduce falls risk in older adults.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study. Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables. Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo. Our results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds.

The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs. The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes. Among 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02). The progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association.

Association polymorphism of guanine nucleotide-binding protein β3 subunit (GNB3) C825T and insertion/deletion of the angiotensin-converting enzyme (ACE) gene with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy-related heart disease. Genetic roles such as gene polymorphisms may relate to the etiology of PPCM. This study analyzes the association between single nucleotide gene polymorphism (SNP) guanine nucleotide-binding protein beta-3 subunit (GNB3) C825T and insertion/deletion (I/D) of the angiotensin-converting enzyme (ACE) gene with the incidence of PPCM. An analytic observational study with a case-control design was conducted at the Integrated Cardiac Service Center of Dr. Soetomo General Hospital, Surabaya, Indonesia. PPCM patients of the case and control groups were enrolled. Baseline characteristic data were collected and blood samples were analyzed for SNP in the GNB3 C825T gene and for I/D in the ACE gene by using the polymerase chain reaction, restriction fragment length polymorphism, and Sanger sequencing. We also assessed ACE levels among different ACE genotypes using a sandwich-ELISA test. A total of 100 patients were included in this study, with 34 PPCM cases and 66 controls. There were significant differences in GNB3 TT and TC genotypes in the case group compared with that in the control group (TT: 35.3% vs. 10.6%, p = 0.003; TC: 41.2% vs. 62.5%, p = 0.022). The TT genotype increased the risk of PPCM by 4.6-fold. There was also a significant difference in the ACE DD genotype in the case group compared with that in the control group (26.5% vs. 9.1%, p = 0.021). DD genotypes increased the risk of PPCM by 3.6-fold. ACE levels were significantly higher in the DD genotype group than in the ID and II genotype groups (4,356.88 ± 232.44 pg/mL vs. 3,980.91 ± 77.79 pg/mL vs. 3,679.94 ± 325.77 pg/mL, p < 0.001). The TT genotype of GNB3 and the DD genotype of the ACE are likely to increase the risk of PPCM. Therefore, these polymorphisms may be predisposing risk factors for PPCM incidence. ACE levels were significantly higher in the DD genotype group, which certainly had clinical implications for the management of PPCM patients in the administration of ACE inhibitors as one of the therapy options.

Association of ACE ID, MTHFR C677T, and MIF-173GC variants with the clinical course of COVID-19 patients

The course of coronavirus disease-2019 (COVID-19) differs from person to person. The relationship between the genetic variations of the host and the course of COVID-19 has been a matter of interest. In this study, we investigated whether Angiotensin-Converting Enzyme (ACE) ID, Methylenetetrahydrofolate Reductase (MTHFR) C677T, and Macrophage Migration Inhibitory Factor (MIF)-173GC variants are risk factors for the clinical course of COVID-19 disease in Turkish patients. One hundred COVID-19 patients were included in the study. The diagnosis of COVID-19 was made using Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Chest Computed Tomography (CT). The patients were evaluated in 3 groups: intensive care, service, and outpatient treatment. ACE ID, MTHFR C677T, and MIF-173GC variants were genotyped by PCR-Restriction Fragment Length Polymorphism (RFLP) methods. When the genotype distribution between the groups was examined, it was found that the frequency of the ACE DD genotype and the D allele was higher in the intensive care group compared to the hospitalized and outpatient groups. MTHFR C677T CT genotype T allele and MIF-173GC, CC genotype C allele were more prevalent in the intensive care group compared to other groups. Patients with PCR-positive results had a higher MTHFR C677T C/C genotype and C allele. In CT-positive patients, the MTHFR C677T CT genotype and the MIF-173GC, G allele were more common. It is predicted that genetic predisposition may contribute to COVID-19 morbidity and mortality. Our results show that ACE ID, MTHFR C677T, and MIF-173GC variants affect the course of COVID-19 disease in the Turkish population.

Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals.

Current research on the angiotensin-converting-enzyme (ACE) gene has yielded controversial results on whether different ACE polymorphisms are linked with human longevity. ACE polymorphisms are a risk factor for Alzheimer's disease and age-onset diseases that may contribute to the mortality of older people. Our goal is to consolidate existing studies, using artificial intelligence-assisted software to come to a more precise understanding of the role of the ACE gene in human longevity. The I (insertion) and D (deletion) polymorphisms in the intron are correlated with the levels of circulating ACE; homozygous D (DD) is high, and homozygous I (II) is low. Here, we performed a detailed meta-analysis of the I and D polymorphisms using centenarians (100+ years old), long-lived subjects (85+ years old), and control groups. ACE genotype distribution was analyzed across a total of 2054 centenarians and 12,074 controls, as well as 1367 long-lived subjects between the ages of 85-99, using the inverse variance and random effects methods. The ACE DD genotype was found to be favored in centenarians (OR: 1.41 (95% CI: 1.19-1.67), p < 0.0001) with a heterogeneity of 32%, and the II genotype slightly favored the control groups (OR: 0.81 (95% CI: 0.66-0.98), p = 0.03) with a heterogeneity of 28%, corroborating results from previous meta-analyses. Novel to our meta-analysis, the ID genotype was found to be favored in control groups (OR: 0.86 (95% CI: 0.76-0.97), p = 0.01) with a heterogeneity of 0%. The long-lived group showed a similar positive association between the DD genotype and longevity (OR: 1.34 (95% CI: 1.21-1.48), p < 0.0001) and a negative association between the II genotype and longevity (OR: 0.79 (95% CI: 0.70-0.88), p < 0.0001). The long-lived ID genotype did not show significant findings (OR: 0.93 (95% CI: 0.84-1.02), p = 0.79). In conclusion, the results suggest a significant positive association of the DD genotype with human longevity. However, despite the previous study, the results do not confirm a positive association of the ID genotype with human longevity. We suggest a few important paradoxical implications: (1) inhibition of ACE can increase longevity in model systems from nematodes to mammals, seemingly opposite to the finding in humans; (2) exceptional longevity associated with homozygous DD is also associated with age-related diseases with higher mortality risks in homozygous DD. We discuss ACE, longevity, and age-related diseases.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in patients with laryngeal cancer.

The aim of this study was to compare the distribution of the angiotensin-converting enzyme (ACE) I/D polymorphism between patients with laryngeal cancer (LC) and a control group and to examine the distribution of this polymorphism with clinical parameters related to LC. We enrolled 44 LC patients and 61 healthy controls. The ACE I/D polymorphism was genotyped with the PCR-RFLP method. The distribution of ACE genotypes (II, ID, and DD) and alleles (I or D) was evaluated with Pearson's chi-square test, and logistic regression analysis was performed for statistically significant parameters. There was no significant difference in ACE genotypes and alleles between LC patients and controls (p = 0.079 and p = 0.068, respectively). Among clinical parameters related to LC (extension of tumour, node metastasis, tumour stage and tumour location), only the presence of node metastasis was found to be significant in terms of ACE DD genotype (p = 0.137, p = 0.031, p = 0.147, p = 0.321 respectively). In the logistic regression analysis, the ACE DD genotype was increased 8.3 fold in nodal metastases. The findings of the study suggest that ACE genotypes and alleles do not affect the prevalence of LC, but the DD genotype of ACE polymorphism may increase the risk of lymph node metastasis in LC patients.

Association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with risk of hypertension among the Ethiopian population.

Although the pathophysiological mechanism of hypertension is not fully elucidated yet, a large number of pieces of evidence have shown that genetic alterations in the renin-angiotensin-aldosterone system play a central role. However, the association of insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene with essential hypertension is controversial yet, and there is a limited number of publications among the Ethiopian population. Therefore, this study aimed to determine the association of ACE gene I/D polymorphism with the risk of hypertension among essential hypertension patients at the University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia. A case-control study was conducted from October 07, 2020, to June 02, 2021, among hypertensive patients and normotensive control groups at the University of Gondar Comprehensive Specialized Hospital. A structured questionnaire was used to collect socio-demographic data and anthropometric measurements. Five milliliters of blood were drawn from each of the randomly selected 64 hypertensive and 64 normotensive participants for molecular test analysis. Genetic polymorphism of the ACE gene was identified using polymerase chain reaction (PCR) and electrophoresis. Data analysis was done using SPSS version 25.0 software. The strength of association between the genotype and hypertension was estimated through the calculation of adjusted odds ratio and 95% confidence intervals using logistic regression. P-value &lt; 0.05 was considered statistically significant. The distribution of DD genotypes and D allele of the ACE gene were 48.4% and 63% in essential hypertensive patients, respectively, while it were 29.7% and 42.2% in control subjects respectively. The ACE DD genotype (p-value = 0.005) and D allele (p-value = 0.001) were more frequent among hypertensive patients as compared to controls. The present study found that the DD genotype and D allele of the ACE gene has had a strong association with a high risk of hypertension in the study population.

The Association Between Variants of Angiotensin Converting Enzyme (ACE) Gene With Risk Factors in Patients with Ischemic Stroke at Dr. Kariadi Semarang

BACKGROUND : Stroke is the leading cause of death and disability in the world. The occurrence of ischemic stroke is indicated by genetic factors, environmental factors and the interaction between it. Angiotensin Converting Enzyme (ACE) genetic variant is associated with various characteristics of risk factors for ischemic stroke.&#x0D; OBJECTIVE : Identifying genetic variants of Angiotensin Converting Enzyme (ACE) with the Polymerase Chain Reaction (PCR) method and to find it’s correlation beetwen risk factor in patients with Ischemic Stroke at Dr. Kariadi Semarang&#x0D; METHOD : The subjects of the study were 72 patients with ishcemic stroke who were treated at the polyclinic of the Neurology Department Dr. Kariadi Semarang in January - December 2013. DNA extraction of research subjects was carried out at the Laboratory of the Center of Biomedical Research (CEBIOR), Faculty of Medicine, Diponegoro University from January to March 2020. Amplification using the Polymerase Chain Reaction (PCR) method was carried out using an Eppendorf thermocycler. Data were analyzed with SPSS for Windows Version 25&#x0D; RESULT : 72 samples analyzed obtained genetic variants of ACE II 39 (54.2%) samples, genetic variants of ACE DI 30 samples (41.7%), and genetic variants of ACE DD 3 (4.2%) samples. Meanwhile, there was no significant relationship ( p&gt;0,05 ) between genetic variants of ACE and the characteristics of risk factors for ischemic stroke, namely age, gender, Body Mass Index, smoking history, triglyceride levels, HDL levels, LDL levels, obesity and hypertension.&#x0D; CONCLUSION : There are three types of ACE genetic variants, including the ACE II genetic variant, the ACE DI genetic variant, and the ACE DD genetic variant. Among the three genetic variants, ACE II genetic variant is the most common variant and there is no significant relationship to the various risk factor characteristics found in ischemic stroke patients at Dr. Kariadi Gneeral Hospital Semarang.

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

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

Angiotensin-converting enzyme-1 gene insertion/deletion polymorphism may be associated with COVID-19 clinical severity: a prospective cohort study

BACKGROUND: Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism may play a role in the pathogenesis of coronavirus-19 disease (COVID-19).OBJECTIVES: Investigate the relationship between ACE I/D polymorphism and the clinical severity of COVID-19.DESIGN: Prospective cohort study.SETTING: Tertiary care hospital.PATIENTS AND METHODS: The study included COVID-19 patients with asymptomatic, mild, and severe disease with clinical data and whole blood samples collected from 1 April 2020 to 1 July 2020. ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis.MAIN OUTCOME MEASURE: ACE DD, DI and II genotypes frequencies.SAMPLE SIZE: 90 cases, 30 in each disease severity group.RESULTS: Age and the frequency of general comorbidity increased significantly from the asymptomatic disease group to the severe disease group. Advanced age, diabetes mellitus and presence of ischemic heart disease were independent risk factors for severe COVID-19 [OR and 95 % CI: 1.052 (1.021-1.083), 5.204 (1.006-26.892) and 5.922 (1.109-31.633), respectively]. The ACE II genotype was the dominant genotype (50%) in asymptomatic patients, while the DD genotype was the dominant genotype (63.3 %) in severe disease. The ACE II geno-type was protective against severe COVID-19 [OR and 95% CI: .323 (.112-.929)]. All nine patients (8.9%) who died had severe disease.CONCLUSIONS: The clinical severity of COVID-19 infection may be associated with the ACE I/D polymorphism.LIMITATIONS: Small sample size and single center.CONFLICT OF INTEREST: None.

Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

RationaleHypertension, obesity and diabetes are major risk factors associated with morbidities underlying COVID-19 infections. Regression analysis correlated presence of ACE insertion/deletion (I/D) polymorphism to COVID-19 incidence and mortality. Furthermore, COVID-19 prevalence correlated to allele frequency of angiotensin-converting enzyme (ACE) deletion (D) polymorphism within the European population.ObjectiveHomozygous ACE deletion polymorphism is associated with increase in ACE and angiotensin II (Ang-II), sustained levels can result in inflammation, fibrosis and organ damage. The ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for COVID-19 infection and outcomes. The study objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities providing rationale for therapeutic utility of ACE-I/ARBs to improve outcomes.Method and ResultsThe Allele Frequency Database (ALFRED) was queried for frequency of rs4646994 representing ACE I/D polymorphism. In a total of 349 worldwide population samples, frequency of ACE D allele was higher in European, Asian, and Africans cohorts. In the USA, the frequency of ACE D allele was higher in non-Hispanic Black compared with non-Hispanic White and Mexican Americans.ConclusionCOVID-19 binding mediated reduction/inactivation of ACE-II can increase ACE/Ang-II signalling pathway and related pathologies. The presence of ACE DD polymorphism with COVID-19 infection likely augments ACE/Ang-II activities, increasing severity of COVID-19 morbidities and impacts outcomes. Thus, ethnic prevalence of ACE DD polymorphism can explain in part the severity of COVID-19 morbidity providing rationale for the use of ACE-I/ARBs to improve outcomes.

Understanding COVID-19: A hypothesis regarding digit ratio (2D:4D), ACE I/D polymorphism, oxygen metabolism and national case fatality rates

ObjectiveMale digit ratio (2D:4D) correlates positively with the national case fatality rate (CFR) for COVID-19. The severity of COVID-19 may be influenced by a counterbalance between the angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2). SARS-CoV2 cleaves with ACE2 and enters cells leaving an unopposed effect of ACE in the lungs. Both 2D:4D and the ACE I/D polymorphism are covariates of oxygen metabolism. COVID-19 leads to lung damage and a reduction in oxygen saturation of the blood. Here, we examine the interrelationships between 2D:4D, ACE polymorphism, and COVID-19 CFR. MethodsNational frequencies/rates were obtained for 2D:4D from the BBC Internet study (n = 41), published values of ACE I/II (n = 39), and COVID-19 CFR from three World Health Organization situation reports (n = 41). Results2D:4D was negatively associated with national ACE I/II frequencies. However, there was a positive relationship between male 2D:4D and CFR (right and left 2D:4D, two, and three situation reports respectively). The relationships between ACE I/II and CFR were non-significant. Relationships between male 2D:4D and CFR's were independent of female 2D:4D and ACE I/II. ConclusionsThe ACE I/D polymorphism may influence 2D:4D such that ACE II individuals have lower 2D:4D than ACE DD individuals. Low 2D:4D and ACE II individuals show efficient oxygen metabolism. Therefore, low 2D:4D and ACE II together may protect against COVID-19 severity. The sex-dependent positive correlation between male 2D:4D and CFR is independent of ACE I/II, suggesting that the sex-dependent variation in the ACE2 gene may also influence the 2D:4D phenotype.

Testing for the Association Between ACE DD (RS1799752) Polymorphism and the Metabolic Syndrome in Patients with Hypertension

High blood pressure (HBP) is a complex multifactorial condition which has a polygenic predisposition. The angiotensin-converting enzyme (ACE) is one of the candidate genes for HBP, and the ACE ID polymorphism with DD genotype presents a high risk for myocardial infarction, obesity (OB), stroke, type 1 diabetes mellitus (DM1), type 2 diabetes mellitus (DM2), diabetic nephropathy. The purpose of the study is to identify the high risk of developing MS in ACE DD gene (RS1799752) on the basis of clinical data, biochemical laboratory investigations, genotyping and sequencing of ACE gene in patients with HBP, by using the mathematical algorithm ANOVA One Way as a linear model, with the help of the MDR, Graph Pad Prism and MATLAB software. This study includes 68 subjects, selected from Giurgiu County Emergency Hospital based on clinical data, biochemical investigations, RFLP-PCR genotyping and Advanced NGx sequencing of the ACE gene with the DD genotype to identify the increased risk of developing metabolic syndrome (MS) in patients with hypertension. The results was taken by using as a linear model the mathematical algorithm ANOVA One Way using the programs MDR, Graph Pad Prism and MATLAB. In conclusion the ACE DD polymorphism is significantly associated with MS in patients with hypertension.

Association Between the Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism and Avascular Necrosis of the Femoral Head.

Objective: This study investigated the association between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and avascular necrosis of the femoral head (ANFH). Materials and Methods: The ACE gene I/D polymorphism was determined in 279 nontraumatic, ANFH Han Chinese patients (divided into idiopathic and steroid- and alcohol-induced subgroups) and 276 age- and gender-matched healthy controls using the polymerase chain reaction. Results: The frequencies of the ACE DD genotype and D allele were significantly higher among the ANFH patients as a whole and also in the idiopathic and steroid- and alcohol-induced ANFH subgroups compared to healthy controls (p < 0.05 for all). Additionally, the DD genotype, compared with the ID+II, ID, and II genotypes, conferred a higher risk of developing ANFH across all clinical subgroups (p < 0.001, odds ratio [OR] = 2.508; p < 0.001, OR = 2.072; p < 0.001, OR = 3.684, respectively) as well in each of the subgroups examined individually, including the idiopathic subgroup (p < 0.001, OR = 2.579; p < 0.001, OR = 2.091; p < 0.001, OR = 3.994, respectively), the steroid-induced subgroup (p = 0.005, OR = 2.345; p = 0.031, OR = 2.050; p = 0.007, OR = 3.000, respectively), and the alcohol-induced subgroup (p < 0.001, OR = 2.488; p = 0.012, OR = 2.050; p = 0.011, OR = 2.659, respectively) of ANFH patients. The ID genotype, compared with the II genotype, conferred a higher risk across all subtypes analyzed together, and in the idiopathic subgroup (p = 0.013, OR = 1.778; p = 0.028, OR = 1.910) analyzed separately. Additionally, the D allele, in comparison with the I allele, conferred a relatively higher risk across all subgroups (p < 0.001, OR = 2.101) as well as in each of the three subgroups examined individually (idiopathic: p < 0.001, OR = 2.178; steroid-induced: p = 0.003, OR = 1.910; and alcohol-induced: p < 0.001, OR = 2.094). Conclusion: The ACE DD and ID genotypes and D allele may be risk factors for susceptibility to ANFH in the Chinese population.

Association of ACE I/D and AGTR1 A1166C Gene Polymorphisms and Risk of Uterine Leiomyoma: A Case-Control Study.

Objective:Uterine leiomyoma (UL) can be considered as the most common benign gynecological tumors of the smooth muscle cells in the myometrium. They are likely to be associated with infertility and recurrent abortion as well as obstructed labor and post-partum hemorrhage. Moreover, altered vascular-related genes can be linked to developing leiomyoma. Polymorphisms of the angiotensin-converting enzyme (ACE) gene are associated with some vascular diseases. The present study was carried out to investigate the association of ACE I/D and AGTR1 A1166C gene polymorphisms and the risk of uterine leiomyoma in a sample of Iranian population. Methods:The study was carried out on a total of 413 women divided into 202 patients with diagnosed uterine leiomyomas and a control group of 211. Genotyping was performed using the PCR or PCR-RFLP methods. Results:The ID and DD genotypes of ACE I/D polymorphism were associated with 2 and 2.9 fold higher risk of UL compared to II genotype (OR, 2 [95% CI, 1.3 to 3.2]; P = 0.004 and OR, 2.9 [95% CI, 1.6 to 5]; P = 0.0002). The frequencies of ACE D alleles were 53.7% in women with UL and 40.3% in controls, which were observed to be statistically different (P < 0.0001). The alleles and genotypes of AGTR1 A1166C polymorphism were not different between UL and control women (P=0.9). Conclusion:The ACE ID and DD genotypes were associated with a higher risk of UL. No relationship was found between AGTR1 A1166C polymorphism and UL.

Effects of 8 weeks of moderate-intensity resistance training on muscle changes in postmenopausal women with different angiotensin-converting enzyme insertion/deletion polymorphisms of interest

The aim of the study was to explore the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and muscle adaptations to moderate-intensity resistance training in postmenopausal women. Forty healthy postmenopausal Chinese women (aged 53-66 years) were recruited and grouped by ACE I/D polymorphism (the homozygous deletion genotype [DD], n = 12; the I allele carriers [II/ID], n = 28). All participants performed an 8-week full-body resistance training program at moderate intensity with 15-repetition maximum. Upper- and lower-limb muscle mass, grip and back strength, anatomical cross-sectional area of the rectus femoris (ACSARF), isokinetic knee extension strength (MVCKE) and knee flexion strength were measured before and after training. Our results showed significant genotype × time interaction in ACSARF and MVCKE (P = 0.007 and P = 0.03, respectively) with the DD group having greater changes in corresponding parameters than the I-allele carriers (P = 0.012 and P = 0.018, respectively). Multivariate linear regression results showed that the ACE DD genotype was positively related to the grip strength adaptation (r = 0.48, P = 0.05). This study improves our understanding of the association between the ACE I/D polymorphism and muscular responses to moderate intensity resistance training among postmenopausal women and revealed that the DD genotype has predominant adaptations in grip strength, rectus femoris size, and knee extensor strength.

Angiotensin-converting enzyme insertion/deletion gene polymorphisms and the risk of glioma in an Algerian population.

IntroductionJust recently, it has been established that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is linked to the pathogenesis and to the evolution of human cancers. Therefore, the present study was concerned with the investigation of an eventual association between glioma and I/D polymorphism of the ACE gene.MethodsThe expression of ACE gene was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis in 36 Algerian patients with glioma and 195 healthy controls.ResultsIn glioma cases, allelic frequencies and genotypes distribution of the ACE I/D polymorphism were different from controls cases. ACE DD genotype were highly presented in glioma cases (63.9%) than controls (33.8%) and conferred 3.64-fold risk for predisposition in glioma cases (vs ID genotype, p<0.001). Recessive model (ACE II + ID genotypes vs DD) was associated with a 72% reduced risk of glioma (OR = 0.28, 95% CI: 0.13-0.60, p <0.001). Per copy D allele frequency was found higher in glioma cases (79.2%) than in controls (63.3 %), OR = 2.20, 95% CI: 1.20 - 4.03, p = 0.009.ConclusionThe obtained data showed that the presence of the D allele might be a risk factor for the development of glioma. Further studies considering different ethnic groups with large samples are required to confirm this finding.

Childhood adiposity, adult adiposity, and the ACE gene insertion/deletion polymorphism: evidence of gene-environment interaction effects on adult blood pressure and hypertension status in adulthood.

Genetic variants may modify the associations of adiposity measures with blood pressure (BP) and hypertension. The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is an attractive candidate. To examine interaction effects between I/D polymorphism and adiposity measures (BMI, waist circumference, waist-to-hip ratio, and skinfold thickness) during childhood and adulthood in relation to adult BP and hypertension. Data were available for 4835 participants from three prospective cohort studies. Multivariable linear regression models for adult SBP and DBP, and multivariable logistic regression models for hypertension were fit that included interaction effects between child or adult adiposity and I/D polymorphism. Evidence for interaction effects on BP/hypertension were found across the three studies. Compared with childhood measures, the effect modification appeared to be more consistent when using adult adiposity. In particular, the adverse effects of greater adult waist circumference on increasing adult SBP and DBP appeared to be larger among carriers of ACE DD (or GG) [adjusted linear regression coefficients 0.26, 95% CI (0.21-0.31) and 0.28 (0.24-0.32) for SBP and DBP, respectively] and ID (or AG) genotypes [0.25 (0.21-0.29) and 0.25 (0.21-0.28), respectively], whereas those with II (or AA) genotypes had smaller effects [0.15 (0.09-0.21) and 0.19 (0.13-0.23)]. ACE genetic variation may modify the effect of adult adiposity on increasing BP and risk of hypertension in adulthood. Individuals with ACE DD (or GG) and/or ID (or AG) genotypes, compared with those with II (or AA) genotype, appear more vulnerable to the impact of excess adiposity.

Association of Angiotensin Converting Enzyme (ACE) Gene Polymorphisms and Risk of Diabetic 2 Among Patients Visiting Bahirdar Felegehiwot Referral Hospital North West, Ethiopia

Background: Type 2 diabetes (T2DM) affect large population. There are many genetic and non genetic factors associated for the occurrence of T2DM. Genes of the renin angiotensin system angiotensin converting enzyme insertion/deletion gene polymorphism has been associated with the risk of type 2 diabetes. The aim of the present study was to investigate the association of angiotensin converting enzyme gene polymorphism, risk of type 2 diabetes. Methods: A total of 222 subjects (111 T2DM and 111 healthy controls) were collected from Bahir Dar Felegehiwot Referral Hospital and Bahir Dar town, respectively by using non-probability purposive sampling techniques. Minidray fully automated analyzer was used for biochemical tests. The ACE I/D genotypes were identified by Polymerase chain reaction (PCR) using appropriate primers and PCR reaction conditions. Results: The present study revealed that the frequency of DD genotype and D allele were higher in type 2 diabetes mellitus compared to healthy controls (DD, 64.2% vs.35.6% P<0.001) and (D, 79.3% vs.59.9% P<0.001). DD genotype showed threefold increase risk towards T2DM as compared to II Genotype (OR: 2.984, CI: 1.332-6.689, P<0.02). The D allele carriers had five times high risk of getting diabetic as compared to I allele. (OR, D 2.178; CI: 1.168-3.232 P<0.001 vs.I OR, 0.459; CI: 0.309-0.681 P<0.001).Conclusion: Нis study indicated that the frequency of ACE DD genotype and D allele were markedly higher in patients with type 2 diabetes