Angiotensin I-converting Enzyme Genotype Research Articles

Seeking for associations of I/D polymorphism of ACE gene with self-reported work performance, memory, and cardiovascular health in a professional leadership community

Introduction. Maintaining labor efficiency, working under conditions of stress and uncertainty, high level of requirements to the functional state of workers in various professions actualize the occupational health study of work performance. Methodological applications of predictive medicine and psychogenetics make it possible to identify specific hereditary (biological) predispositions of individuals, to carry out professional orientation of a person, to provide humanistic recommendations on occupation of a certain type of professional activity.
 The study aims to identify a correlation between ACE genotypes and work performance capability in individuals from a professional leadership community.
 Materials and methods. Individuals from a professional leadership community, after dividing into two cohorts consisting of entrepreneurs and non-entrepreneurs, were interviewed and genotyped for evidence of genotype-by-insertion/deletion (I/D) polymorphism associations of the angiotensin I converting enzyme (ACE) gene and health status. Answers to 4 questions characterized the state of work performance and memory, and another 4 questions characterized the cardiovascular system. The mean age was 37±1.7 years for entrepreneurs and 34.23±0.66 years for non-entrepreneurs. There were 44 females and 129 males among them.
 Results. Analysis of genotyping of 173 people (25 entrepreneurs and 148 non-entrepreneurs) revealed a significant deviation of actual frequencies of I and D alleles from theoretically expected values in the whole group of managers and between non-entrepreneurs (p=0.95, χ2>3.8). In all groups, there was a marked increase in the frequency of the I/I genotype at the expense of a decrease in the frequency of the D/D genotype compared to the literature data. A significant difference between D/D and I/D genotypes in work performance was found in entrepreneurs (p=0.9817), which coincides with a significant difference between their representatives by age (p>0.99). Contrary to expectations, representatives of the D/D genotype, at least entrepreneurs, demonstrated the most optimal level of functioning of the autonomic nervous system. No associations were found between the genotype for the ACE gene (rs4646994) and work performance and memory.
 Conclusion. In the total sample of leaders and among the subgroup of non-entrepreneurs, a strong and reliable change in the frequencies of alleles I and D was found compared to the theoretically expected (frequencies). There was a significant increase in the frequency of I/I genotype in all groups. The significant difference in the rates between the D/D and I/D groups coincides with a significant difference between their representatives in terms of age. According to the results of test answers, representatives of entrepreneurs of D/D genotype had the most optimal level of vegetative nervous system functioning.

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

BackgroundAdiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood.MethodsThis study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12–30 from Taiwan.ResultsResults showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (− 0.095 vs. − 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG.ConclusionsIn this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Is Angiotensin Converting Enzyme Insertion/Deletion (rs1799752) Polymorphism Associated with Breast Cancer Risk in Egyptian Population?

Background: According to GLOBOCAN estimates, breast cancer was found to be the most often diagnosed cancer in women worldwide, (11.7 %) and the fourth leading cause of cancer mortality (6.9 %).
 Aim: The purpose of this study is to investigate the role of the Angiotensin I-converting enzyme (ACE) gene polymorphism in breast cancer prediction risk in Egyptian population.
 Methods: Polymorphism detection analysis was performed on 163 subjects from breast cancer (BC) patients, 79 with Benign Breast Disease group (BBD) patients and 202 controls (C). ACE I/D (rs1799752) polymorphism were detected using polymerase chain reaction (PCR).
 Results: The observed genotype frequencies were II 10.9%, ID 78.2% and DD 10.9% in healthy control, II 8.6%, ID 79.1% and DD 12.3% in BC patients and II 12.6%, ID 78.4% and DD 9% in BBD patients. There were no association between ACE gene polymorphisms, between the BC or BBD groups when compared to the control group (ORDD= 1.43, 95 % CI= (0.58-3.52), P= 0.29) and (ORDD= 1.29, 95 % CI= (0.57-2.95), P= 0.37) respectively. There was no risk estimate in BC or BBD when DD vs II + ID (Recessive) or ID vs II+ DD (Over-dominant) were compared to control. Allele frequencies show the same figure. From the different histological BC hormonal markers the Her2 was showing significant association in ID genotype of ACE I/D (rs1799752) (P= 0.04) and dominant model (II vs ID + DD, P= 0.03). Concerning different BC prognostic models, the poor prognostic one of Her2 enriched model (ER-ve PR-ve Her2+ve) show significant association in ACE genotype ID and dominant model (II vs ID + DD), (P= 0.01) when compared to the good prognostic hormonal status.
 Conclusion: It seems that this is the first study that interested in correlate the ACE gene polymorphisms in different BC variants characters in Egyptian patients. ACE I/D (rs1799752) polymorphism ID genotype have strong association to breast cancer carcinogenesis, poor prognosis and metastasis. It may be used as practical biomarker to guide the BC carcinogenesis and risk process.

The Relationship of Angiotensin I-Converting Enzyme Genotype to Liver Fibrogenesis in Non-Alcoholic Steatohepatitis

AbstractBackground: Multiple genetic and environmental factors may lead to fibrogenesis in patients with Non-alcoholic fatty liver (NAFL). Many studies investigated the relation of angiotensin I-converting enzyme (ACE) genotyping to liver fibrosis in chronic liver disease; and the results are contradic-tory.Aim of Study: In the current study, ACE genotype was assessed in NAFLD patients to show its possible association with development liver fibrosis.Subjects and Methods: The study included 162 patients of NAFLD disease, 49 (30.25%) patients with mild fibrosis, 65 (40.12%) with moderate fibrosis and 48 (29.63%) with severe fibrosis in addition to 138 volunteers was enrolled as a healthy controls. All patients and controls were investigated to serum glucose and fasting insulin level and HOMA-IR was calculated. Liver function tests, both serum ACE and trans-forming growth factor-beta (TGF-b) were done. ACE geno-typing [insertion/deletion (I/D)] was done by PCR.Results: Fasting glucose and insulin, HOMA-IR, AST, ALT and GGT were significantly higher in NAFLD patients than healthy controls. The homozygous frequency I/I and D/D or D/I of ACE were not significantly different between NAFLD patients and controls. The D/D genotype was associated significantly with the severity of liver fibrosis, D/I polymor-phism with moderate fibrosis and I/I genotype with mild fibrosis. The higher D allele frequency was associated with severe fibrosis, while I allele was frequent in mild fibrosis. The HOMA-IR, ALT, serum ACE and TGF-b were increased significantly in the patients carrying D/D homozygous gene more than those carrying homozygous I/I or D/I polymorphism. The serum ACE and TGF-b were significantly higher in NAFLD patients compared to control and the most higher levels was reported in cases with severe liver fibrosis than moderate and mild liver fibrosis.Conclusion: ACE (D/D) genotype was closely associated with liver fibrosis severity and ACE (I/D) polymorphism was observed in moderate stage of fibrosis. The allele D is seems to be a risk factor for liver fibrosis development than allele I. The knowledge of the ACE genotypes in NAFLD patients may be important for treatment decision in those patients and beneficial in the follow-up of the disease progression.

Associations of ACE I/D polymorphism with the levels of ACE, kallikrein, angiotensin II and interleukin-6 in STEMI patients

This study aimed to compare the plasma levels of angiotensin-I converting enzyme (ACE), Angiotensin II (AngII), kallikrein (KLK1) and interleukin-6 (IL-6) in ST segment elevation myocardial infarction (STEMI) patients with different ACE Insertion/deletion (I/D) polymorphisms in a Chinese population. The ACE genotypes were determined in the 199 STEMI patients and 216 control subjects. STEMI patients were divided into three groups based on the ACE genotypes. Single polymerase chain reaction (PCR) was performed to characterize ACE I/D polymorphisms. Plasma levels of ACE, AngII, KLK1 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). We found that the DD or ID genotype was significantly independently associated with high ACE (OR = 4.697; 95% CI = 1.927–11.339), KLK1 (3.339; 1.383–8.063) and IL-6 levels (OR = 2.10; 1.025–4.327) in STEMI patients. However, there was no statistical significance between the ACE I/D polymorphism and AngII plasma levels whether in univariate or multivariate logistic regression. Additionally, we detected a significantly positive correlation between plasma KLK1 levels and IL-6 levels in STEMI patients (r = 0.584, P < 0.001). The study showed high levels of ACE, KLK1 and IL-6 were detected when the D allele was present, but AngII plasma levels was not influenced by the ACE I/D polymorphism.

PO-008 Influences of ACE I/D and ACTN3 R577X polymorphisms in elite female soccer athletes

Objective The performance phenotype is regulated by polygenes .There were few reports about the cumulative effect of the I/D polymorphism in the angiotensin I-converting enzyme (ACE) gene and ACTN3 in athletes.This study was to investigate the association of ACEI/D and ACTN3 R577X polymorphisms with the performance of Chinese elite female soccer athletes for the first time. &#x0D; Methods The genotype distributions of ACE I/D and ACTN3 R577X in the athlete group (N=92) and the control group of Chinese females (N=200) were evaluated via PCR and compared.&#x0D; Results Regarding the distribution of ACE polymorphisms, the genotype frequency was indifferent between the athletes (II 40.2%, ID 46.7%, DD 13.1%) and the controls (II 42%, ID 48%, DD 10%) based on the chi-square test. No difference in the I/D allele frequency was observed between the athlete group (I allele: 59.25%; D allele: 40.75%) and the control group (I allele: 60.8%; D allele: 39.2%). Regarding the distribution of ACTN3 polymorphisms, the genotype frequency was significantly different between the athletes (XX 0%, XR 53.3%, RR 46.7%) and the controls (XX 16%, XR 44%, RR 40%). The allele frequency was observed no different between the athlete and the control group (X allele:34.8%/41.7%; R allele: 65.2%/58.3%, respectively). The ACE and ACTN3 genotype combinations (II/ID/DD+RR/XR) significantly differed between the athletes and the controls by χ2 test (p&lt;0.05).&#x0D; Conclusions These results suggested that the Chinese elite female soccer athletes were more likely to harbor the I allele and the R allele and that the combination of ACE II/ID and ACTN3 RR/XR was a synergetic determinant of the athletic performance of females in soccer.

ACE insertion/deletion polymorphism and restenosis events after coronary stent placement in East Azerbaijan Province of Iran

Renin-angiotensin system is thought to play a role in coronary thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. The association among restenosis within coronary stents, the D/I polymorphism is analyzed in the present study. We are selected 50 patients who had undergone successful percutaneous transluminal coronary angioplasty, and angiography during 1 year after it for some reason. The I/D alleles were identified on the basis of polymerase chain reaction (PCR) amplification of the respective fragments from intron 16 of ACE gene. The differences between groups were tested by Chi-square test or Fisher exact test. Result from chi-square test and Fisher exact test shows the lack of differences between two groups with respect to sex, age, diabetes, hypertension, cholesterol, hyperlipidemia, stent type, length of stented segment, stent diameter and target vessel. In the second set of analysis, the relationship between genotypes and the outcome variable was tested. These analyses indicated that there were no statistically significant differences the three groups (χ2 (2) = 1.40, p=0 .47). The ACE D/D genotype or D allele does not influence the clinical and angiographic outcome of patients undergoing coronary stent placement. These data suggest that routine determination of the ACE genotype may not help identify patients who are at a higher risk of thrombotic and restenosis events after coronary stent placement.

Changes in Food Group and Nutrient Intakes Following a DNA‐based Dietary Advice Intervention for Sodium Intake

A recent randomized controlled trial demonstrated that DNA‐based dietary advice improved dietary compliance to sodium recommendations to a greater extent than general dietary recommendations. While sodium intake is a public health concern, little is known about changes to diet quality when individuals reduce their sodium intake. The objective of the present study was to investigate changes in food group and nutrient intakes following dietary sodium reduction. Subjects aged 20–35 years (n=138) completed a baseline food frequency questionnaire (FFQ) and were randomized to an intervention (I) or control (C) group. Those in the I group were genotyped for the angiotensin‐I converting enzyme (ACE) gene, which is associated with salt‐sensitive hypertension, and were given DNA‐based advice for sodium intake based on their ACE genotype. The C group was given a general recommendation for sodium intake without genetic information. Another FFQ was collected 12 months after the intervention. General linear models with a Tukey‐Kramer post‐hoc test for multiple comparisons were conducted to examine changes in intakes of food groups and dietary intakes of macronutrients and micronutrients. Compared to the C group, subjects in the I group who carried the risk version of ACE significantly reduced their intake of meat and alternatives (servings/day) (‐0.34 ± 0.13 [I] vs. 0.13 ± 0.16 [C], p=0.04). Significant reductions were also observed for intakes of cholesterol (mg/day) (‐32.9 ± 17.9 [I] vs. 14.4 ± 20.9 [C], p=0.04) and fiber (g/day) (‐0.8 ± 1.5 [I] vs. 3.1 ± 1.8 [C], p=0.01). These results demonstrate the effect of dietary sodium reduction on other aspects of diet quality.

Angiotensin I-converting enzyme gene polymorphism enhances the effect of hypercholesterolemia on the risk of coronary heart disease in a general Japanese population: the hisayama study.

The angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been reported to be implicated in susceptibility to coronary heart disease (CHD). However, this association remains inconclusive. The purpose of this study was to clarify the association between the I/D polymorphism of the ACE gene and the development of CHD in a Japanese general population and investigate whether the effects of traditional risk factors on the risk of CHD are heterogeneous among ACE genotypes. The subjects included 2,125 community-dwelling individuals 40 years of age or older without cardiovascular disease for whom genetic information was available. All patients were prospectively followed for 19 years, and the association between the ACE polymorphism and the incidence of CHD was examined based on the interactions with traditional risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking. A total of 161 CHD events occurred during the follow-up period. The age- and sex-adjusted incidence of CHD was not significantly different among the genotypes (5.8, 5.2, and 6.9 per 1,000person-years for genotypes II, ID and DD, respectively). In a stratified analysis, however, the ACE DD genotype was found to significantly accelerate the risk of developing CHD by hypercholesterolemia (hazard ratio [HR]=4.50, 95% confidence interval=2.02-10.04 for hypercholesterolemia with the DD genotype; HR=1.48, 95% CI=1.04-2.12 for hypercholesterolemia with the ID＋II genotype; P for interaction=0.01), even after adjusting for other confounding factors, whereas no such associations were observed for hypertension, diabetes or smoking. The current findings suggest that the ACE DD genotype enhances the effect of hypercholesterolemia on the development of CHD in the general Japanese population.

Association of Angiotensin-Converting Enzyme Genotype, Insertion/Deletion Polymorphism and Saphenous Vein Graft Atherosclerosis in Iranian Patients.

OBJECTIVE The aim of this study was to evaluate possible interactions among Angiotensin-I converting enzyme genotype, insertion/deletion polymorphism and atherosclerosis of vein grafts in Iranian patients, and characterize their clinical and demographic profile.METHODS In this cross-sectional study, patients who underwent coronary artery bypass graft surgery more than five years ago, were included for angiographic analysis. Atherosclerosis was determined by quantitative angiography and adjusted Gensini score. The gene angiotensin converting enzyme I/D polymorphism was detected by polymerase chain reaction.RESULTS A total of 102 patients participated in this study. Eighty-four patients were male. The frequency distribution of DD, ID and II polymorphism were 23.6%, 62.7% and 13.7% respectively. There were no differences among genotypic groups in age, sex, number of risk factors, number of vein grafts and months since bypass surgery. According to adjusted Gensini score [0.18±0.12 (II) vs. 0.11±0.09 (ID) and 0.1±0.09 (DD) P=0.021] the II genotype was associated with severity of vein graft atherosclerosis.CONCLUSION Although there are conflicting results about gene angiotensin converting enzyme I/D polymorphism and the degree of venous bypass graft degeneration, this study suggests an association between ACE genotype II and atherosclerosis of saphenous vein grafts, however, large samples considering clinical, demographic and ethnic profile are necessary to confirm these results.

Association of angiotensin I-converting enzyme gene insertion/deletion polymorphism with rheumatic heart disease in Indian population and meta-analysis

Rheumatic heart disease (RHD) is one of the most severe consequences of rheumatic fever. It has been suggested that angiotensin I-converting enzyme (ACE) may be involved in the increased valvular fibrosis and calcification in the pathogenesis of RHD. We conducted a case-control study to look for association of ACE I/D polymorphism with RHD in Indian population. The study incorporated 300 patients (170 males and 130 females) with RHD, and 200 controls (118 males and 82 females). We also subgrouped RHD patients into mitral valve lesion (MVL) and combined valve lesion (CVL). ACE I/D polymorphism was identified using polymerase chain reaction method. We also performed a meta-analysis of three published studies and the present study (636 RHD cases and 533 controls) to evaluate the association between the ACE I/D polymorphisms and RHD risk. A significant difference in ACE ID and DD genotypes distribution between RHD cases (OR = 1.62, 95% CI = 1.11-2.36 and OR = 2.08, 95% CI = 1.02-4.15, respectively) and corresponding controls was observed. On comparing the ACE genotypes of MVL and CVL subgroups with controls, ID and DD genotypes were also significantly associated with CVL (FDR Pcorr = 0.009, OR = 2.19 and FDR Pcorr = 0.014, OR = 3.29, respectively). Meta-analysis also suggested association of the ACE D allele (FDR Pcorr = 0.036, OR-1.22, 95% CI 1.02-1.45) with RHD. In conclusion, ACE ID and DD genotypes are associated with an increased risk of RHD, particularly CVL. This suggests that the ACE I/D gene polymorphism may play an important role in the pathogenesis of RHD.

A randomized controlled trial of genetic information on dietary intake

Personal genetic information has become obtainable as a result of commercial genetic tests, but its effect on dietary change is not clear. We compared the effects of providing DNA‐based dietary advice with general recommendations on dietary intake using a randomized trial. Subjects aged 20–35 years (n=102) completed a baseline food frequency questionnaire (FFQ) and were randomized to an intervention (I) or control (C) group. Subjects in the intervention group were genotyped for the angiotensin‐I converting enzyme (ACE) gene, which has been associated with salt‐sensitive hypertension, and were given personalized advice for sodium intake based on their ACE genotype. The control group was given a general recommendation for sodium intake without genetic information. A second FFQ was collected 3 months later. A significant reduction in sodium intake was observed in subjects in the intervention group who were informed that they carried the risk allele for ACE when compared to the control group (−174.9±89.1 mg/day [I] vs. 225.5±123.5 mg/day [C]; p = 0.008). No difference was observed between subjects who were informed that they did not carry the risk allele and controls (111.2±145.0 mg/day [I] vs. 225.5±123.5 mg/day [C]; p = 0.48). The results suggest that personalized advice based on genetic information may be superior to general advice in motivating individuals to adopt dietary changes.Grant Funding Source: Advanced Foods and Materials Network

The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training

Alternative measures of muscle size, strength, and power to those used in previous studies could help resolve the controversy surrounding associations between polymorphisms of the angiotensin-I converting enzyme (ACE) and α-actinin-3 (ACTN3) genes and skeletal muscle phenotypes, and the responses to resistance training (RT). To this end, we measured quadriceps femoris muscle volume (Vm), physiological cross-sectional area (PCSA), maximum isometric force (Ft), specific force (Ft per unit PCSA), maximum isoinertial strength (1-RM), and maximum power (Wmax ; n = 40) before and after 9-week knee extension RT in 51 previously untrained young men, who were genotyped for the ACE I/D and ACTN3 R577X polymorphisms. ACTN3 R-allele carriers had greater Vm, 1-RM, and Wmax than XX homozygotes at baseline (all P < 0.05), but responses to RT were independent of ACTN3 genotype (all P > 0.05). Muscle phenotypes were independent of ACE genotype before (all P > 0.05) and after RT (all P > 0.01). However, people with the "optimal" ACE+ACTN3 genotype combination had greater baseline 1-RM and Wmax compared to those with the "suboptimal" profile (both P < 0.0125). We show for the first time that the ACTN3 R577X polymorphism is associated with human Vm and (independently and in combination with the ACE I/D polymorphism) influences 1-RM and Wmax.

The insertion/deletion polymorphism in the ACE gene and chronic obstructive pulmonary disease

An insertion/deletion (I/D) polymorphism was identified in intron 16 of the gene encoding the human angiotensin I-converting enzyme (ACE), a candidate gene for chronic obstructive pulmonary disease (COPD). We investigated the relationship between this polymorphism in the ACE gene and the risk of developing COPD. Sixty-six COPD in-patients and 40 non-smoking control individuals were recruited for this study. The distribution of ACE genotypes in these individuals was studied. The frequencies of ACE genotypes were found to be 47.0% for DD, 30.3% for ID, and 22.7% for II in the COPD group and 32.5% for DD, 47.5% for ID, and 20.0% for II in the control group. The allele frequencies were found to be 0.62% for the D allele and 0.38% for the I allele in the COPD group and 0.56% for the D allele and 0.44% for the I allele in the control group. A significant difference was found between I and D allele frequencies (P < 0.05) of the study and control groups. Our results suggest that this ACE polymorphism may be associated with the development of COPD.

Angiotensin converting enzyme (ACE D/I) polymorphism and its relation to liver fibrosis progression in Egyptian patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection is a global health problem in Egypt and causes different liver disease spectrum. Evidence indicates that angiotensin I converting enzyme (ACE) gene polymorphism may play a role in determining disease progression. We aimed to determine the association of ACE gene I/D polymorphism with ACE serum levels and to examine the association between different I/D genotypes with the severity of hepatic fibrosis in chronic HCV infected Egyptian patients. Thirty controls and 90 HCV infected patients participated in the study, patients were subgrouped by Ishak stage of fibrosis into subgroup IIa (n=30; fibrosis score 0–1), subgroup IIb (n=38; fibrosis score 2–3) and subgroup IIc (n=22; fibrosis score 4–6). DNA was multiplied by polymerase chain reaction (PCR). ACE genotype frequency in HCV infected patients was significantly different comparing to controls (X2=7.169, P=0.028). With non-significant difference in ACE D/I genotypes and allele frequencies among the patient subgroups (P>0.05),the frequency of the DD, DI and II genotypes in subgroup IIa, subgroup IIb and subgroup IIc were (53.3%, 36.6%, 10%), (44.7%, 44.7%, 10.5%) and (50%, 22.7%, 27%), respectively. The D and I allele frequency were (71.66%, 28.33%), (67.1%, 32.9%) and (61.36%, 38.63%), respectively. ACE serum levels were significantly increased in DD more than DI and II (t=2.56, 3.43, P<0.05), respectively, with non-significant association in sonographic findings, viral load and liver function test (LFT) parameters with the ACE genotypes. Serum ACE levels were significantly increased in all patient subgroups when compared to controls with a non significant difference of ACE levels between subgroup IIb and IIc. We concluded that the D/D genotype is associated with HCV infection but not associated with degree or the progression of hepatic fibrosis.

Gene Polymorphism in Angiotensin-I-Converting Enzyme and Physical Activity Among Normotensive Chinese

The angiotensin-I-converting enzyme (ACE) I/D gene polymorphism has been studied for its role in determining habitual physical activity level, but there is no information from Asian populations. The objective of this study was to determine whether this ACE gene polymorphism was associated with physical activity level among Chinese in Singapore. In this cross-sectional study, 110 normotensive Chinese in Singapore, age 21-61 yr, completed the short-form version of the International Physical Activity Questionnaire and contributed buccal cell samples for genotyping of the ACE I/D gene polymorphism using polymerase chain-reaction amplification. They also provided demographic information and underwent anthropometric measurements. Physical activity level was expressed as continuous (in kcal/wk) and categorical (low, moderate, or high) data. The 3 genotypes of ACE were DD (homozygous for the deletion allele), II (homozygous for the insertion allele), and ID. Among the participants, 28.2% reported low, 49.1% moderate, and 22.7% high physical activity level. Frequencies of the genotypes were 11.8% for DD, 42.7% for ID, and 45.5% for II. ACE genotype was independently associated with physical activity level. After age, gender, and body-mass index were adjusted for, individuals with DD or ID genotypes were more likely to report insufficient or low physical activity level than those with II genotypes (odds ratio = 6.88; 95% confidence interval: 2.26, 20.94). In conclusion, the I/D polymorphism of the ACE gene is significantly associated with self-reported physical activity level in normotensive Chinese Singaporeans.

The Alu polymorphism of angiotensin I converting enzyme (ACE) and atherosclerosis, incident chronic diseases and mortality in an elderly Chinese population.

We examined the contribution of ACE I/D polymorphism in a large Chinese population to four year change in ankle-brachial index (ABI), development of cardiovascular diseases and mortality in a prospective study adjusting for many confounding factors. Data are drawn from a longitudinal study of 4000 community-living men and women aged 65 years and over, for which detailed information regarding lifestyle, chronic diseases, body mass index (BMI), ABI measurements and ACE polymorphisms were documented at baseline. During the fifth year of follow up, incident cardiovascular diseases, ABI, and mortality were documented, and related to ACE genotype adjusting for age, smoking, alcohol, dietary intake, physical activity, body mass index, and use of ACE inhibitors. Women with the D/D genotype had the greatest reduction in mean ABI after adjusting for confounding factors. D/D genotype was also more common among women who developed hypertension or myocardial infarction. However D/D genotype was associated with mortality only in men. In a Chinese elderly population, ACE polymorphism may be considered "deleterious" to longevity, the D/D genotype being associated with mortality, the atherosclerotic process, hypertension and myocardial infarction. There are gender differences in the relationship between D/D genotype and cardiovascular diseases and mortality may not be mediated by the atherosclerotic process alone.

Serum angiotensin I-converting enzyme response to exercise; no differential effect of genotype

Angiotensin I-converting enzyme (ACE) plays a pivotal role in whole body fluid balance and the degradation of bradykinin. A common allelic variant with a 287 base pair insert has been...

No Association of Angiotensin I Converting Enzyme I/D Polymorphism with Domain-Specific Cognitive Function in Aged Men without Dementia

Previous research studies have related the insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene to cognitive function in various neuropsychiatric or neurodegenerative disorders, but not yet investigated its genetic association with specific cognitive domains. Thus, the aim of this study was to assess the possible association of the ACE I/D polymorphism with domain-specific cognitive function in normal cognitive aging. Four hundred and sixty-nine-aged ethnic Chinese men without dementia were enrolled for genotyping and evaluated using several neuropsychological tests [Mini-Mental Status Examination (MMSE), Digit Span Forward and Backward, and Cognitive Ability Screening Instrument Chinese language version (CASI C-2.0)]. No direct association was found between ACE genotypes and the MMSE, Digit Span tests, or CASI total scores. Although subjects with I/I genotype had the lowest cognitive performance in the CASI visual construction domain (P=0.031), this statistical difference disappeared after correction for multiple comparisons. This study suggests that the ACE I/D polymorphism does not have any genetic association with global or specific cognitive domain in aged men without dementia.

The ACE Gene and Human Performance

Some 12 years ago, a polymorphism of the angiotensin I-converting enzyme (ACE) gene became the first genetic element shown to impact substantially on human physical performance. The renin-angiotensin system (RAS) exists not just as an endocrine regulator, but also within local tissue and cells, where it serves a variety of functions. Functional genetic polymorphic variants have been identified for most components of RAS, of which the best known and studied is a polymorphism of the ACE gene. The ACE insertion/deletion (I/D) polymorphism has been associated with improvements in performance and exercise duration in a variety of populations. The I allele has been consistently demonstrated to be associated with endurance-orientated events, notably, in triathlons. Meanwhile, the D allele is associated with strength- and power-orientated performance, and has been found in significant excess among elite swimmers. Exceptions to these associations do exist, and are discussed. In theory, associations with ACE genotype may be due to functional variants in nearby loci, and/or related genetic polymorphism such as the angiotensin receptor, growth hormone and bradykinin genes. Studies of growth hormone gene variants have not shown significant associations with performance in studies involving both triathletes and military recruits. The angiotensin type-1 receptor has two functional polymorphisms that have not been shown to be associated with performance, although studies of hypoxic ascent have yielded conflicting results. ACE genotype influences bradykinin levels, and a common gene variant in the bradykinin 2 receptor exists. The high kinin activity haplotye has been associated with increased endurance performance at an Olympic level, and similar results of metabolic efficiency have been demonstrated in triathletes. Whilst the ACE genotype is associated with overall performance ability, at a single organ level, the ACE genotype and related polymorphism have significant associations. In cardiac muscle, ACE genotype has associations with left ventricular mass changes in response to stimulus, in both the health and diseased states. The D allele is associated with an exaggerated response to training, and the I allele with the lowest cardiac growth response. In light of the I-allele association with endurance performance, it seems likely that other regulatory mechanisms exist. Similarly in skeletal muscle, the D allele is associated with greater strength gains in response to training, in both healthy individuals and chronic disease states. As in overall performance, those genetic polymorphisms related to the ACE genotype, such as the bradykinin 2 gene, also influence skeletal muscle strength. Finally, the ACE genotype may influence metabolic efficiency, and elite mountaineers have demonstrated an excess of I alleles and I/I genotype frequency in comparison to controls. Interestingly, this was not seen in amateur climbers. Corroboratory evidence exists among high-altitude settlements in both South America and India, where the I allele exists in greater frequency in those who migrated from the lowlands. Unfortunately, if the ACE genotype does influence metabolic efficiency, associations with peak maximal oxygen consumption have yet to be rigorously demonstrated. The ACE genotype is an important but single factor in the determinant of sporting phenotype. Much of the mechanisms underlying this remain unexplored despite 12 years of research.