Angiotensin-converting Enzyme Genotype Research Articles

Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study

BackgroundAngiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality. MethodsWe undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from ‘Worldometer’. Multivariable analyses were also undertaken adjusting for age (median age), sex (percentage of females) and the number of COVID-19 tests undertaken. Associations between genotypes deletion/deletion (DD) and insertion/insertion (II) prevalence and COVID-19-related mortality (per million people per day since the first diagnosed case) were evaluated. ResultsThe frequency of II genotype is highest in east Asian countries and lower among the European and African countries. An inverse geographical distribution frequency was noted for DD genotype. Increasing II genotype frequency was significantly associated with decreased COVID-19 mortality rates (adjusted incident rate ratio [IRR] 0.3, 95% confidence interval [CI]: 0.002–0.7, p = 0.03). However, no association was found between DD genotype frequency and COVID-19 mortality rates (adjusted IRR 4.3, 95% CI: 0.5–41.2, p = 0.2). ConclusionsDistribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality. This information has potential utility for resource planning at a systemic level, as well as for clinical management.

Relationship of angiotensin converting enzyme (I/D) polymorphism (rs4646994) and coronary heart disease among a male Iraqi population with type 2 diabetes mellitus.

Insertion deletion (I/D) polymorphism (rs4646994) in the angiotensin-converting enzyme (ACE) has a substantial effect on coronary heart disease (CHD). The amplification of an Alu repetitive element in an intron of the ACE has shown three potential genotypes of I/I and D/D as homozygous, and I/D as heterozygous. The objective of this study was to investigate the association between the ACE gene polymorphism and CHD among male Iraqi patients with and without type2 diabetes mellitus (T2DM). A case-control study of total 217 male subjects participated in this study, divided into three groups; Group 1 including 86 CHD patients with T2DM, group 2 including 78 CHD patients without T2DM, and group 3 including 53 age and sex-matched healthy individuals (as a control group). Genotyping of ACE (I/D) gene was performed using polymerase chain reaction (PCR) technique. The II allele was significantly more frequent in CHD patients without T2DM compared to the control population, but not from those patients with T2DM (p < 0.05). Nonetheless, the ID allele was significantly more frequent in each of CHD with T2DM and control populations compared to the CHD without T2DM. The DD allele was significantly more frequent in CHD patients with T2DM compared to each of CHD patients without T2DM and control populations (p < 0.05). We conclude that the D/D and I/D genotypes are implicated as risk factors for development of CHD with T2DM, but not CHD without T2DM among the male Iraqi population. However, larger sample sizes are needed to monitor the CHD patients and to validate this study.

Lack of association between angiotensin-converting enzyme (ACE) genotype and essential hypertension in Peruvian older people

Background: Epidemiological studies have shown an association between the ACE gene I/D polymorphism with arterial hypertension, specifically the DD genotype, in different populations. The objective of this study is to evaluate the association between ACE polymorphisms (Insertion, Deletion or I/D) and essential hypertension in a population of Lima, Peru. Material and methods: This is a study of cases (essential arterial hypertension) and controls, with determination of the ACE I/D genotype. Results: Cases (65) and controls (39) had a mean age (standard deviation) of 74.3 (7.9) and 72.6 (6.5) (p = 0.24). In cases, the genotype frequencies DD, ID, and II were 6 (9.2%), 28 (43.1%) and 31 (47.7%), respectively. In controls, the genotype frequencies DD, ID, and II were 6 (15.4%), 14 (35.9%) and 19 (48.7%). The Hardy-Weinberg equilibrium analysis in cases and controls was p = 0.93 and p = 0.23, respectively. No significant associations between genotype DD vs. ID + II (OR = 0.56, 95% CI: 0.17–1.87, p = 0.34) or II vs. DD + ID (OR = 0.95, 95% CI: 0.43–2.12, p = 0.92) and essential hypertension were found. Conclusions: The ACE I/D polymorphism was not associated with hypertension in our sample.

A Pooled Study of Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphism in Relation to Risk, Pathology and Prognosis of Childhood Immunoglobulin A Vasculitis Nephritis.

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism has been inconsistently reported to be a risk factor for Childhood immunoglobulin A vasculitis (IgAV) nephritis. We comprehensively searched electronic databases as of Jan 2020. Nineteen studies with 1104 cases and 1589 controls were included. Sensitivity analyses based on different subgroups were performed. Further analyses were conducted for association of ACE polymorphism with disease severity and prognosis. Significant associations were found between ACE I/D polymorphism and childhood IgAV nephritis, with the strongest association in DD vs. II comparison (OR 1.72, 95% CI 1.21-2.46). Subgroup analyses generally showed significant results. Besides, ACE polymorphism was significantly associated with proteinuria (DD + DI vs. II: OR 2.22, 95% CI 1.14-4.33; DI + II vs. DD: OR 0.49, 95% CI 0.30-0.81) and worse prognosis (the strongest effect in DD + DI vs. II: OR 4.43, 95% CI 1.84-10.71) among children with IgAV nephritis. The ACE polymorphism seemed not to be associated with hematuria, hypertension, and renal pathology. This study suggested significant association of ACE gene polymorphism with the risk of IgAV nephritis in children. D allele in the ACE genotype could be a useful genetic marker to predict proteinuria and worse prognosis for childhood IgAV nephritis.

Angiotensin Converting Enzyme Gene Polymorphism in Dyslipidemia and Hypertension

ABSTRACT Background: Hypertension and dyslipidemia have a multifactorial background based on genetic and environmental interactive factors. Increasing blood pressure (BP) and hypertension incidence have also been found to be linked with elevated blood lipids rates. Insertion/deletion (I/D) polymorphisms of the angiotensin converting enzyme (ACE) are said to be linked to pathogenesis of both hypertension and dyslipidemia. Objectives: to investigate the presence of the three genotypes of ACE gene (I/D) polymorphisms with hypertension and dyslipidemia. Subjects and methods: Participants included 30 Egyptian patients with hypertension and /or dyslipidaemia (Group I) and 20 apparently healthy controls (Group II). For all participants, DNA was isolated and amplified by polymerase chain reaction (PCR); the product was recognized by gel electrophoresis according to their size. Results: diferent ACE genotypes frequencies were detected according to the presence or absence of 287 bp fragment in intron 16; 30% for Deletion/Deletion (DD), 56.7% for Insertion/Deletion (ID) and 13.3% for Insertion/Insertion (II) in patients group, denoting that (I) allele has a significant association with hypertension and dyslipidemia (p < 0.05). Conclusions: There is increased frequency of ACE I/D and I/I, therefore, the I allele was common among Egyptian patients affected with hypertension and /or dyslipidaemia.

Effects of Dexmedetomidine and ACE Genotype on Cardiovascular Response During the Decannulation Period of General Anesthesia in Patients With Essential Hypertension

PurposeThis study investigated the effects of dexmedetomidine on cardiovascular response during the decannulation period of general anesthesia in patients with different genotypes of angiotensin-converting enzyme (ACE) and essential hypertension. MethodsThe present study enrolled patients with essential hypertension and American Society of Anesthesiologists class II or III who were scheduled to undergo abdominal surgery under general anesthesia. Patients were assigned to 1 of 6 groups according to ACE genotype, as detected by polymerase chain reaction–restriction fragment length polymorphism, as follows: DD; ID; II; and DD, ID, and II each with dexmedetomidine (Dex). Dexmedetomidine was intravenously infused at 0.5 μg/kg/h for 30 min before the end of surgery in groups DD (Dex), ID (Dex), and II(Dex). Anesthesia was induced and maintained by the same anesthetics in all patients. Systolic and diastolic blood pressure, heart rate (HR), ECG, and rate-pressure product were recorded before anesthesia induction; at 30 min before the end of surgery; at the end of surgery; and at 0, 1.5, 5, and 10 min after extubation. FindingsA total of 210 patients were enrolled (n = 35 per genotype). After extubation, systolic and diastolic blood pressure, HR, and RPP were increased markedly from baseline in groups DD, ID, and II; the increases were greater in groups DD and ID than in group II. No significant changes in blood pressure, HR, or RPP were found, and proper sedative was achieved in groups DD (Dex), ID (Dex), and II(Dex). The prevalences of cardiac arrhythmia were higher in groups DD and ID than in groups II, DD (Dex), ID (Dex), and II(Dex). ImplicationsPatients essential hypertension and the ACE D allele had a strong hemodynamic response to tracheal extubation, on which dexmedetomidine was found to have both a prevention and treatment effect

Angiotensin-converting enzyme gene D-allele and the severity of coronary artery disease.

Coronary artery disease (CAD) is the first cause of morbidity and mortality worldwide. An important goal is to diagnose patients in early stages, in order to reduce acute cardiovascular events. The angiotensin-converting enzyme (ACE) is an important element for the cardiovascular system, through its actions on hydro-salin balance and vascular tone. ACE polymorphism consists of insertions (I)/deletions (D) and there are 3 genotypes: II, ID, DD. It is speculated that the DD genotype may be a genetic basis for severe CAD, while the II genotype may have a protective effect on the coronary arteries. The present study included 154 patients with acute coronary syndroms admitted to the Institute for Cardiovascular Disease 'George I.M. Georgescu', Iasi. The patients underwent coronary angiography in order to assess the severity of the lesions and the ACE genotypes were determined for each patient. The genotypes were correlated with the severity of the vessel-disease and the exposure to classic risk factors. It was concluded that the D-allele is associated with a greater risk for acute coronary events and severe coronary stenosis, especially when risk genotype and risk phenotype interact.

Coronavirus Disease 2019 and Hypertension: The Role of Angiotensin-Converting Enzyme 2 and the Renin-Angiotensin System.

Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of severe acute respiratory syndrome coronavirus 2, the virus responsible for COVID-19, into host cells. Because RAS inhibitors have been suggested to increase ACE2 expression, health-care providers and patients have grappled with the decision of whether to discontinue these medications during the COVID-19 pandemic. However, experimental models of analogous viral pneumonias suggest RAS inhibitors may exert protective effects against acute lung injury. We review how RAS and ACE2 biology may affect outcomes in COVID-19 through pulmonary and other systemic effects. In addition, we briefly detail the data for and against continuation of RAS inhibitors in persons with COVID-19 and summarize the current consensus recommendations from select specialty organizations.

Acute Responses of Cardiac Biomarkers to Intermittent and Continuous Exercise Are Related to Age Difference but Not I/D Polymorphism in the ACE Gene.

PurposeThe purpose of this study was to determine the (i) cardiac biomarker (cTnI and NT-proBNP) responses to moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) in the middle-aged and young groups, (ii) relationship of post-exercise cardiac biomarker release between these two age groups, and (iii) investigate whether insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is associated with predisposition to cardiac damage after exercise in Iranian men.MethodsWe examined cTnI and NT-proBNP in 29 middle-aged (54.5 ± 4.6 years) and 28 young (22.7 ± 4.2 years) soccer players before and after HIIE and MICE running tests.ResultsThe middle-aged soccer players had higher baseline cTnI (0.015 ± 0.007 ng/ml vs. 0.010 ± 0.006 ng/ml; P = 0.01) and NT-proBNP (30.7 ± 13.6 ng/L vs. 18.4 ± 8.3 ng/L; P < 0.001) values compared with the young group. The changes with exercise (ΔcTnI: 13 vs. 11 ng/ml and ΔNT-proBNP: 18 vs. 11 ng/L) were also higher in the middle-aged group. No subject exceeded the upper reference limit for cTnI and NT-proBNP. Considering three ACE genotypes, the mean cTnI and NT-proBNP values of middle-aged and young groups did not show any significant difference.ConclusionMarked differences in baseline and post-exercise cTnI and NT-proBNP values were observed, which were related to age differences but not to ACE genotypes.

Angiotensin converting enzyme polymorphism and ischemic stroke.

Objectives:To assess the polymorphism of angiotensin converting enzyme (ACE) in ischemic stroke in an Egyptian sample.Methods:One hundred subjects (70 ischemic stroke patients, and 30 healthy controls) were included in case control cross sectional study during the period from January 2017 to January 2018, at Neurology Department, Menufia University Hospital, Shibin EL-Kom, Egypt. Patients underwent complete neurological assessment, national institute health stroke scale (NIHSS), and Toast classification. All subjects underwent genotyping of ACE gene polymorphism.Results:There are 42.9% from the patients versus 33.3% from controls showed geno typing of Insertion/Deletion (I/D) and Allele D is more frequent regarding I allele in ischemic stroke patients but this difference did not reach significant level to be risk factor. The I/D polymorphism was the predominant type in SVS and LVS while DD was the predominant type in cardio-embolic one. There were no significant differences between NIHSS in different ACE gene polymorphism.Conclusion:In spite of ACE genotyping differences among Egyptian ischemic stroke patients, we cannot consider it a predisposing factor to stroke occurrence or severity.

Genetic Association of ACE Polymorphism with Sarcopenia and Effects of Genetic Regulation of ACE Activity on Muscle Function

The purpose of this study was to investigate associations between skeletal muscle mass and ACE polymorphism, or sarcopenia‐related candidate gene, and to examine the effects of genetical angiotensin‐converting enzyme (ACE) activity on physical performance and respiratory muscle function in Korean adults. For this study, 1,464 Korean adults aged 18~79 were recruited. The anthropometrics were 1.69±0.06m (height), 63.1±5.5kg (weight), 29.4±6.5% (percent body fat), and 24.5±3.0kg/m2 (body mass index). Fat‐free mass, physical performance, gait speed (Timed Up‐and‐Go), pulmonary function (maximal inspiration and expiration pressure) and fatiguing maximum voluntary isometric contraction (40% MVIC) of ankle plantar flexor muscles with dynamic Electromyography were tested. Data of body composition and muscle functions were analyzed using one‐way ANOVA and post‐hoc Scheffe test for continuos variables and the Chi‐square test and host‐hoc Bonfferioni correction for countable variables. Blood samples for the whole blood and serum were obtained and assayed for circulating ACE activity and the ACE I/D genotype. The distribution of ACE polymorphism throughout the groups was analyzed using the Chi‐square test and host‐hoc Bonferroni correction for genetic distribution and multiple logistic regression analysis for the odds ratios (ORs) with 95% confidence intervals (CIs). We found that the distribution of ACE Indel genotype for sarcopenia was significantly different from normal population who have normal or high fat‐free mass index. Especially, we found a significantly higher (p&lt;.05) distribution of DD genotype in sarcopenia participants (27%) than the incidence (12.5%) in normal population. The D allele of ACE genotypes in older adults indicated significantly slower gait speed than I allele of them in the Timed Up‐and‐go test (p&lt;.05), and significantly lower levels for maximal inspiration and expiration pressure (p&lt;.05). The II genotype in older adults indicate the highest tolerance of muscle fatigue during muscle contraction (p&lt;.05). In conclusion, ACE Indel polymorphism and level of ACE activity is associated with sarcopenia in older adults and would genetically regulate muscle function in part. Our findings suggest that genetical concentrations of angiotensin‐converting enzyme should play a role in determining low muscle mass, slow walking speed, respiratory muscle function, and fatigue after muscle contraction in individuals. Therefore, examining ACE Indel polymorphism and ACE activity level could be used to predict sarcopenia and muscle function, and subsequently this information can be applicable to prevention and treatment to the aging muscle.Support or Funding InformationThis research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (358‐2011‐1‐G00025).

The Impact of Angiotensin-Converting Enzyme Gene on Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease.

The Angiotensin-Converting Enzyme (ACE) gene has drawn attention for its possible role in regulating the degradation of β-amyloid (Aβ), yet its role in affecting the cognitive and psychiatric symptoms of Alzheimer`s Disease (AD) patients has yet to be elucidated. This study aimed to investigate whether the ACE gene acts as a risk factor of Behavioral and Psychological Symptoms of Dementia (BPSD) in the AD population. The genotyping of ACE and Apolipoprotein E gene with allele ε4(APOEε4) was determined among 360s clinically diagnosed AD patients. Symptoms and severity of BPSD were evaluated annually via Neuropsychiatric Inventory (NPI). At the base measurement of the first year of patient recruitment, there were no significant contributory risk factors to NPI score. In the two-year follow-up, ACE insertion polymorphism showed a significant risk (adjusted odds ratio=1.65, 95% CI=1.1- 2.5, p=0.019) of progression of NPI total score. ACE gene is involved in aggravating BPSD among AD patients.

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.

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.

Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population.

The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

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. ‎

ACE insertion/deletion genetic polymorphism, serum ACE levels and high dietary salt intake influence the risk of obesity development among the Saudi adult population

Introduction:Angiotensin-converting enzyme (ACE), which contributes to adipocyte growth, differentiation and function, has recently been linked with both salt metabolism and obesity development. Therefore, this study has aimed to investigate the putative relationship between ACE genetic polymorphism, serum ACE levels and salt consumption on the risk of developing obesity in the Saudi population.Materials and methods:ACE genotype status of 267 adult Saudi volunteers (124 obese and 143 non-obese) was correlated with their serum ACE activity and dietary salt intake amounts.Results:Obesity was more prevalent in deletion-deletion genotype individuals (p<0.03), under dominant, co-dominant and monoallelic conditions (p<0.04). Deletion allele corresponds to serum ACE activity in obese patients (p<0.05). The amount of salt intake (<6 g/d) was significantly associated with obesity and particularly high in deletion-deletion and insertion-deletion genotype carriers (p<0.001). STITCH analysis underlined interactions of the ACE protein with sodium molecule, REN, ACE2, KNG1 and AGTR1 in a biological network.Conclusions:Our findings suggest the positive association between ACE deletion genotype, serum ACE activity and sodium intake with risk of obesity development in the Saudi population.

Genetic Association of Angiotensin-Converting Enzyme (ACE) Gene I/D Polymorphism with Preterm Birth in Korean Women: Case-Control Study and Meta-Analysis.

Background and Objectives: The ACE gene encodes the angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system. Increased ACE activity may cause abnormal regulation of placental circulation and angiogenesis, resulting in adverse pregnancy outcomes. Previous studies have reported that the insertion/deletion (I/D) polymorphism of the ACE gene is associated with the development of preterm birth (PTB). However, results of the association between ACE gene I/D and PTB are inconsistent in various populations. Therefore, we performed a case-control study and a meta-analysis to evaluate the association between ACE I/D polymorphism and PTB. Materials and Methods: We analyzed a total of 254 subjects (111 patients with PTB and 143 women at ≥38 weeks gestation) for the case-control study. For the meta-analysis, we searched Google Scholar, PubMed, and NCBI databases with the terms “ACE,” “angiotensin-converting enzyme,” “preterm birth,” “preterm delivery,” and their combinations. Results: Our results of the case-control study indicated that ACE I/D polymorphism is significantly associated with PTBs in the overdominant genetic model (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.347–0.949, p = 0.029) and that the ID genotype of ACE I/D polymorphism has a protective effect for PTB (OR 0.57, 95% CI 0.333–0.986, p = 0.043). Similarly, the meta-analysis showed that the OR for the ACE gene ID genotype was 0.66 (95% CI 0.490–0.900, p < 0.01). Conclusion: The ACE gene ID genotype has a significant association with PTB and is a protective factor for PTB. A larger sample set and functional studies are required to further elucidate of our findings.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism, Lower Extremity Strength, and Physical Performance in Older Adults.

Evidence for associations between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and physical performance is conflicting. Furthermore, investigations of relationships between lower extremity strength and physical performance have usually not considered the role of the ACE genotype, and it is unclear whether there are variations in relationships between lower extremity strength and physical performance among ACE genotypes in older adults. The objectives of this study were to investigate associations between the ACE I/D polymorphism and physical performance and to determine whether relationships between lower extremity strength and physical performance vary among ACE genotypes in older adults. This was a cross-sectional observational study. Community-dwelling adults (N=88) who were at least 60 years old completed physical performance and lower extremity strength tests. After DNA was extracted from saliva, ACE I/D polymorphism genotyping was done. The Spearman rank order correlation coefficient was used to examine associations between lower extremity strength and physical performance within ACE genotype subgroups. Analysis of covariance and linear regression were used to examine ACE genotype and ACE genotype×lower extremity strength interaction effects in relation to physical performance. Genotype-specific correlation coefficients exhibited substantial variation among ACE genotype subgroups; however, differences did not attain statistical significance. Statistically significant genotype×lower extremity strength interaction effects in relation to physical performance were detected. The cross-sectional design precludes inferring causal relationships between strength and performance. The small sample size contributed to limited power to detect additional interaction effects and to detect statistically significant differences between correlation coefficients among ACE genotype subgroups. The ACE I/D polymorphism is, interactively with lower extremity strength, associated with physical performance. Genotype-specific correlation coefficients and ACE genotype×lower extremity strength interaction effects on physical performance are consistent with variations in relationships between lower extremity strength and performance among ACE genotype subgroups.

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.