Angiotensin-converting Enzyme Genotype Distribution Research Articles

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 polymorphism with diabetic nephropathy in patients using lisinopril

Angiotensin Converting Enzyme (ACE) plays an important role in the development and progression of Diabetic nephropathy (DN). The present study was designed to determine the possible association between ACE gene polymorphism and DN. The study included 242 samples: DN (n = 121), type 2 Diabetes mellitus (DM2) (n = 60) and control (n = 61). The blood samples were collected from the subjects, followed by DNA extraction. Insertion deletion polymorphism of ACE gene studied using specific primers. Patients using Lisinopril were followed for two months. The ACE genotype distribution in DN patients was as follows: DD (n = 47; 38.84%), II (n = 17; 14.04%) and DI (n = 57; 47.10%). In DM group the genotype distribution was DD (n = 4; 6.66%), II (n = 25; 41.66%) and DI (n = 31; 51.66%) while in control group DD (n = 38; 62.29%), II (n = 1; 1.63%) and DI (n = 22; 36.06%). The comparison of II genotype to DD genotype was reflected by p-value =0.0001, OR=17.28 and 95% CI 5.313-49.58. The percent decrease of micro-albuminuria after two months with the use of Lisinopril 10 mg twice a day in DD, II and DI genotype of DN were 31.27%, 12.37% and 16.81%, respectively. Our findings revealed that DD genotype has strong association with DN but not a risk factor for development of disease.

A meta-analysis on the association of ACE and PPARA gene variants and endurance athletic status.

Genetics has an important role in determining the athletic ability and endurance performance potential. This study aimed to investigate the variable results obtained from endurance athletes and control participants in terms of angiotensin-converting enzyme (ACE) and peroxisome proliferator-activated receptor alpha (PPARA) polymorphism distributions. Multiple electronic databases were investigated independently by two researchers. A meta-analysis was conducted on the association of ACE insertion/deletion (I/D) polymorphism and PPARA G/C polymorphisms with endurance athletes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Twenty-six studies were identified for the ACE I/D for 2979 endurance athletes and 10048 control participants while seven studies were identified for PPARA G/C for 901 endurance athletes and 2292 control participants. There was a significant difference in ACE genotype distribution between endurance athletes and control (II vs. ID+DD: OR=1.48; 95% CI=0.30-2.67; P=0.001). On the other hand, there was not a significant difference in PPARA G/C polymorphism genotype distribution between endurance athletes and control (GC+CC vs. GG: OR=0.93; 95% CI=-0.46-2.32; P=0.192; GC+GG vs CC: OR=0.62; 95% CI=-1.75-2.99; P=0.604). The results have shown that ACE I/D polymorphism may be associated with endurance performance in sports and that the predominance of the ACE II genotype in a person may play an advantageous role in being an endurance athlete. However, this effect has not been observed in PPARA G/C polymorphism.

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. ‎

Genotype Distribution of Angiotensin I- Converting Enzyme in Iraqi Arab Population

The angiotensin-converting enzyme (ACE) gene in humans has an insertion-deletion (I/D) polymorphic which produce three allelic variants: II, ID &amp; DD that associated with population relativity and relation with many genetic disease. The polymorphisms of ACE gene were investigated using polymerase chain reaction. The results showed a high frequency of the DD allele among the Iraqi Arab populations (50%), which is similar to those obtained from previous studies for Arab populations. More ever the distribution of ACE genotype among male and female (n= 100, 53male &amp; 47 female) showed DD: 47.17%, II: 22.6% &amp; ID: 30.19% in the male group and DD: 40.43%, II: 17.02% &amp; ID42.55:% in the female group. Significant association of hypertension &amp; diabetic with D allele of the ACE gene has been in Iraqi Arab population

The insertion/deletion polymorphism in the angiotensin-converting enzyme gene and nicotine dependence in schizophrenia patients.

We investigated the relationship between the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the risk of nicotine dependence in Croatian schizophrenia patients. We also tested whether interactions between ACE-I/D polymorphism and smoking status affected the clinical psychopathology findings in patients as measured using Positive and Negative Symptom Scale (PANSS) scores. Polymerase chain reaction analysis was used to genotype 267 chronically ill schizophrenia patients (140 males/127 females). There were no significant differences in the distribution of ACE genotypes and alleles in male or female schizophrenia patients who were stratified based on their smoking status. However, there was a trend toward a difference in the ACE genotype distribution in female smokers vs. nonsmokers (χ 2=5.13, p=0.077) that was due mainly to the significant overrepresentation of ACE-ID heterozygous genotypes in female smokers compared to nonsmokers (62.3 vs. 42.0%, p=0.025). ACE-ID heterozygous females had about a twofold higher smoking risk than ACE-II and ACE-DD homozygous carriers (OR=2.29, 95% CI 1.1-4.7, p=0.026). We observed no contribution of the ACE genotype-smoking interaction to PANSS psychopathology. This is the first study to investigate the possible association between ACE-I/D polymorphism and nicotine dependence in schizophrenia. Our results suggest that the ACE-I/D polymorphism may be relevant in determining the risk of nicotine dependence in female patients with schizophrenia while the ACE genotype-smoking interaction does not contribute to the clinical expression of schizophrenia.

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients.Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed.Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05).Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

Background & objectives:Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD.Methods:In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction.Results:All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD.Interpretation & conclusions:The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.

Characterization of the Relationship between APOBEC3B Deletion and ACE Alu Insertion

The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE), commonly associated with many diseases, is believed to have affected human adaptation to environmental changes during the out-of-Africa expansion. APOBEC3B (A3B), a member of the cytidine deaminase family APOBEC3s, also exhibits a variable gene insertion/deletion polymorphism across world populations. Using data available from published reports, we examined the global geographic distribution of ACE and A3B genotypes. In tracking the modern human dispersal routes of these two genes, we found that the variation trends of the two I/D polymorphisms were directly correlated. We observed that the frequencies of ACE insertion and A3B deletion rose in parallel along the expansion route. To investigate the presence of a correlation between the two polymorphisms and the effect of their interaction on human health, we analyzed 1199 unrelated Chinese adults to determine their genotypes and other important clinical characteristics. We discovered a significant difference between the ACE genotype/allele distribution in the A3B DD and A3B II/ID groups (P = 0.045 and 0.015, respectively), indicating that the ACE Alu I allele frequency in the former group was higher than in the latter group. No specific clinical phenotype could be associated with the interaction between the ACE and A3B I/D polymorphisms. A3B has been identified as a powerful inhibitor of Alu retrotransposition, and primate A3 genes have undergone strong positive selection (and expansion) for restricting the mobility of endogenous retrotransposons during evolution. Based on these findings, we suggest that the ACE Alu insertion was enabled (facilitated) by the A3B deletion and that functional loss of A3B provided an opportunity for enhanced human adaptability and survival in response to the environmental and climate challenges arising during the migration from Africa.

Relation of RAS Gene Polymorphisms with Impaired Glucose Tolerance in Patient with End Stage Renal Failure

Renin angiotensin system (RAS) is a system that is the role of renal hemodynamics, blood pressure and fluid electrolyte balance regulation with progression to end-stage renal disease (ESRD). Angiotensin II (AII),the main mediator of this system, is thought to cause a functional impairment in insulin receptor and post receptor signaling pathways. Our aim; was to show the relation of angiotensin-converting enzyme (ACE), angiotensin II receptor type 1 (AT1 R) and angiotensinogen gene (AGT) polymorphisms, that cause genetic susceptibility to over activation of RAS, to glucose intolerance in patient with end stage renal failure. The study included one hundredth patients. Based on fasting plasma glucose values and oral glucose tolerance test second hours glucose values, patients were grouped as normal patients and patients with glucose intolerance (impaired fasting glycemia (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM)). Insulin resistance was calculated by HOMA-IR method and insulin sensitivity index was calculated by ISI-S method. ACE, AT1 R, AGT polymorphisms were detected by polymerase chain reaction (PCR) method. There was no statistically significant difference between distribution of ACE, AT1R and AGT genotypes and glucose intolerance groups, and insulin resistance. There was a statistically significant difference between MM and TT genotypes and average insulin resistance values (p < 0,04). We have obtained results suggesting a relation between ACE gene D allele and glucose intolerance in patients with end stage renal failure (p=0.06). Moreover, a relation has been shown between AGT gene T allele and insulin resistance (p=0.04).

G Protein β3 Subunit Gene C825T and Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphisms in Hypertensive Tunisian Population

We investigated the interaction between the G protein beta3 subunit (GNB3) C825T variant and angiotensin converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism in hypertensive Tunisian population. Analyses of ACE and GNB3 genotypes were performed in 388 hypertensive patients and 425 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The plasma ACE activity was determined by a spectrophotometric method. The ACE genotype distribution and allele frequencies were not significantly different between the hypertensive and normotensive subjects (p > 0.05). This polymorphism was not associated with hypertension (HTA) (OR = 0.93, 95% CI = 0.75 - 1.15; p = 0.50). In cases, subjects carrying the DD genotype exhibited higher plasma ACE activity than those with ID and II genotypes (p = 0.001). In this group, a linear regression analysis revealed that the ACE I/D polymorphism is independently associated with plasma ACE activity (p = 0.017). The genotypic distribution and allelic frequencies of the GNB3 C825T polymorphism were not significantly different between the two groups. This polymorphism was found to have no effect on the risk of HTA (OR = 1.14, 95% CI = 0.93 - 1.39; p = 0.21). We did not observe a significant interaction between the GNB3 gene and the ACE gene with HTA. In this study, the I/D polymorphism is a significant independent predictor for variability of plasma ACE activity but the ACE I/D and GNB3 C825T polymorphisms are not significant factors for HTA in the Tunisian population. Moreover, we found no interaction between ACE D allele and GNB3 825T allele solely or combined with respect to HTA in the Tunisian population.

Relationship of angiotensin converting enzyme gene polymorphism with diabetic retinopathy

To investigate the association between angiotensin converting enzyme (ACE) gene locus rs1799752 insertion/deletion (I/D) polymorphism and diabetic retinopathy (DR) in type 2 diabetes mellitus. Case-control study. Type 2 diabetes patients were recruited and assigned into DR group, which included proliferative diabetic retinopathy (PDR) group or diabetes without retinopathy (DWR) group. Volunteers without diabetes from the same community were recruited as the control group. PCR and agarose gel electrophoresis methods were adopted to determine the rs1799752 I/D polymorphism genotypes of the ACE gene. The frequency of genotypes and alleles was compared among the various groups. Four hundred and twelve diabetes patients: (207 subjects of DR, including 53 subjects of PDR and 205 subjects of DWR) and 97 non-diabetic control subjects were included in the study. The frequencies of the I and D alleles of ACE rs1799752 polymorphism were 54.1% and 45.9%, respectively, in the DR group, 52.8% and 47.2% in the PDR group, and 48.0% and 52.0% in the DWR group. There were no statistical differences between DR and DWR groups (χ(2) = 3.02, P > 0.05) or between PDR and DWR groups (χ(2) = 0.77, P > 0.05). Moreover, there were no statistical differences in the distribution of the ACE genotypes between DR group (II 25.1%, ID 58.0%, DD 16.9%) and DWR group (II 22.0%, ID 52.2%, DD 25.9%) (χ(2) = 4.92, P > 0.05) or between PDR group (II 20.7%, ID 64.2%, DD 15.1%) and DWR group (χ(2) = 3.19, P > 0.05). No statistical differences were found in the frequencies of the I and D alleles, and the distributions of I/D genotypes between diabetic group and the control group (χ(2) = 0.25, 4.98; P > 0.05). In the multiple regressions model including clinical factors such as the age of onset of diabetes, urinary albumin, insulin usage, creatinine, glycated hemoglobin, fast glucose, and the use of ACE inhibitor, no association was found between ACE gene polymorphism and DR (OR = 0.80, 95%CI: 0.59 - 1.09) or PDR (OR = 1.23, 95%CI: 0.78 - 1.93). There is no association between ACE rs1799752 gene insertion/deletion (I/D) polymorphism and DR in patients with type 2 diabetes mellitus.

Higher Frequency of the ACTN3 R Allele + ACE DD Genotype in Japanese Elite Wrestlers

In this study, the authors investigated the association between the ACTN3 and angiotensin-converting enzyme (ACE) genotypes and the performance of 135 Japanese elite male wrestlers. Fifty-two wrestlers had participated in world championships, including the Olympic Games, or had placed first in Japanese national championships and were classified as "international." The remaining 83 wrestlers were classified as "national." The control group consisted of 333 healthy Japanese college students majoring in physical education. In the ACTN3 genotype distribution, a significant difference between the international and control groups was observed (p < 0.05). The ACE genotype distribution and allele frequency of all wrestlers significantly differed from those of the control subjects (p < 0.001). As compared with the control group, the odds ratio of the ACTN3 R allele + ACE DD genotype being international or national was 3.85 (95% confidence interval [CI], 2.10-7.03) or 1.37 (95% CI, 0.79-2.36), respectively. Our data suggest that the combination of ACTN3 and ACE gene polymorphisms is associated with the athletic status of Japanese elite wrestlers.

Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves

The angiotensin-converting enzyme (ACE) is highly expressed in the aneurysmal vascular wall, in both animal models and human disease. Genetic variations in ACE could be crucial in determining the risk of thoracic aortic aneurysm (TAA). The aim of the present study was to examine the role of ACE insertion/deletion polymorphism on the risk of TAA in patients with bicuspid aortic valves or tricuspid aortic valves. We enrolled 216 patients (158 men; age, 58.9±14.9 years) with TAA, associated with bicuspid aortic valves (n=105) and tricuspid aortic valves (n=111) compared with 312 patients (252 men; age, 54.6±11.0 years) with angiographically proven coronary artery disease and 300 healthy controls (91 men; age, 40.4±10.5 years). The genotype distribution of ACE insertion/deletion was significantly different between the patients with TAA compared with both the control group (P=.0005) and the coronary artery disease group (P=.03). The genotypes were not different between the control group and the coronary artery disease group (P=.3). Compared with the controls, both the bicuspid aortic valve patients (P=.0008) and tricuspid aortic valve patients (P<.0001) had a greater frequency of allele D. The aortic diameters were significantly different among the three genotypes (48.3±6.6, 45.3±8.9, 39.9±8.7 for the DD, DI, and II genotypes, respectively; P=.0002). A synergistic effect between the ACE D allele and hypertension was found for both an increased aortic diameter (P=.003) and the risk of TAA (P<.001). On multivariate logistic regression analysis, D allele (odds ratio, 3.0; 95% confidence interval, 1.1-8.1; P=.03) was a significant predictor of TAA. ACE insertion/deletion polymorphism represents a genetic biomarker for TAA. These findings could have a significant effect on both the early detection and effective pharmacologic treatment of aortic disease.

Angiotensin converting enzyme (ACE) gene polymorphism increases the susceptibility of diabetic nephropathy in Western Indian Type 2 diabetic patients

Angiotensin-converting enzyme (ACE) gene has been associated with the pathogenesis and progressi on of chronic kidney diseases. Diabetic nephropathy has b ecome leading cause of renal end stage disease (ESRD). An I/D polymorphism of angiotensin-converting enzyme (ACE) gene has been suggested as one of the risk factors for the progression of diabetic nephropathy. We analyzed th e genotype and allele frequency distribution of ACE g ene in 166 Type 2 diabetic patients without any complicati on (T2DM), 61 with diabetic nephropathy (DN), 50 with non- diabetic nephropathy (NDN) and 50 healthy individ uals from western Indian population. ACE genotype was analyzed by PCR method. The D allele distributio n for the ACE I/D polymorphisms was not significantly different between control group and patients with T2DM without any complication (41.0% vs. 45.2%, P= 0.461) and between control subjects and patients with non-diabetic nep hropathy (NDN) (41.0% vs. 44.0%, P= 0.668). Frequency of the D allele (63.9% vs. 45.2%, P < 0.001) and DD genotype (I allele noncarrier) (44.3% vs. 25.3%, P= 0.006) of ACE gene was significantly higher in patients with diab etic nephropathy (DN) than in patients with T2DM without any complication. Results of the present study in dicate that ACE gene polymorphism does not have significant influ- ence on development of diabetes mellitus and nondia betic nephropathy, whereas, the DD polymorphism in ACE gene has been associated with the development of diabeti c nephropathy in the Western Indian population.

Angiotensin-converting enzyme deletion allele is beneficial for the longevity of Europeans

The human angiotensin converting enzyme (ACE) gene is one of the most investigated candidate genes for cardiovascular diseases (CVD), but the understanding of its role among the elderly is vague. Therefore, this study focuses at: (a) testing the association of ACE polymorphism with CVD risk factors among the elderly, and (b) detecting the possible unequal distribution of ACE genotypes between senescent and younger segments of the European populations. The association of ACE I/D polymorphism with CVD health status [hypertension (HT), obesity, dislypidemia] in 301 very old subjects (88.2 ± 5 years; F/M = 221/80) was tested by means of logistic regression analysis. The meta-analysis of D allele frequency in general vs. elderly (80+ years) groups was conducted using all publicly available data for European populations comprising both age cohorts. Multiple multinomial logistic regression revealed that within this elderly sample, age (younger olds, 80-90 years), female sex (OR = 3.13, 95% CI = 1.59-6.19), and elevated triglycerides (OR = 2.53, 95% CI = 1.29-4.95) were positively associated with HT, while ACE polymorphism was not. It was also established that the DD genotype was twice as high in 80+ cohort compared to general population of Croatia (p < 0.00001). This trend was confirmed by the meta-analysis that showed higher D allele frequencies in olds from nine of ten considered European populations (OR = 1.19, 95% CI = 1.08-1.31). The data in elderly cohort do not confirm previously reported role of ACE DD genotype to the development of HT. Moreover, meta-analysis indicated that ACE D allele has some selective advantage that contributes to longevity in majority of European populations.

Effects of Prolonged Exercise on Left Ventricular Mechanical Synchrony in Long-Distance Runners: Importance of Previous Exposure to Endurance Races

Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and altered cardiac function on echocardiography. It is not known if cardiac synchrony is altered by prolonged exercise. The aims of this study were to assess changes in intra-left ventricular mechanical synchrony and circulating levels of cardiac troponin following prolonged exercise and to evaluate the importance of prior exposure to endurance racing. Forty-three male participants in a 30-km cross-country race (20 new participants at this event [median, 3 previous endurance races] age matched against 23 repeat participants [median, 31 previous endurance events]) were assessed prospectively 1 to 2 days before and 24 hours after the race using troponin T and Doppler tissue imaging analyzing the standard deviation of time to peak myocardial systolic velocity (T(s)-SD) in a six-basal, six-midventricular segment model measuring myocardial synchrony. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene was also analyzed, as I allele carriers reportedly have superior endurance performance, while the D allele predisposes to renin-angiotensin system-induced cardiac remodeling. Prerace troponin T was undetectable in all runners, and postrace levels were higher in new runners (median, 0.03 microg/L; interquartile range [IQR], 0.01-0.04 microg/L) than in repeat runners (median, 0.01 microg/L; IQR, 0.01-0.02 microg/L) (P = .03). Although new and repeat runners had similar T(s)-SD at baseline (32 msec [IQR, 22-43 msec] vs 34 msec [IQR, 29-45 msec], P = .13), dyssynchrony increased only in new runners (40 msec [IQR, 31-47 msec], P < .001; in repeat runners, median, 38 msec [IQR, 29-43 msec], P = .30; median relative difference, +13% vs +5%, P = .02). ACE genotype distribution was similar in both groups. Multivariate analysis showed that (1) a lack of prior endurance exposure; (2) more copies of the ACE D allele; and (3) lower peak systolic velocity were independent predictors of postrace dyssynchrony (P < .05 for all). Prolonged exertion increased ventricular mechanical dyssynchrony in new endurance participants and in ACE D allele carriers. The long-term impact of such changes warrants future study.

Türkiye’nin Doğu Bölgesinde Auralı ve Aurasız Migren Hastalarında Anjiyotensin Konverting Enzim Geninin İnsersiyon/Delesyon Polimorfizmiyle İlişkisi Var mıdır?

Objective: Angiotensin-converting enzyme (ACE) is one of the key enzymes in the renin-angiotensin-aldosterone system which modulates vascular tension and blood pressure. Many authors have reported an association between ACE-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Alterations of the renin-angiotensin system have been implicated in the pathogenesis of various diseases. Several angiotensin I converting enzyme inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. Previous reports showed an association between migraine without aura and ACE-D allele polymorphism. In this study it is aimed to evaluate whether the DD genotype could also be associated with the frequency and duration of migraine without aura (MoA) and migraine with aura (MwA). Material and Methods: One hundred one migraine patients (37 MoA, 64 MwA) and 101 healthy non-migrainous controls from the region of Eastern Turkey were included in this study. The genotype characteristics were determined by the PCR analysis using DNA extracted from peripheral blood. Results: There was no significant difference in allelic frequency (I and D) and genotype polymorphism (DD, DI and II) of the ACE gene in migraine patients and controls (genotype frequency: p= 0.08). ACE genotype distribution was similar in migraine patients and healthy control groups. Turkish patients MoA and MwA did not show any difference in incidence of the ACE-DD genotype. Conclusion: We conclude that the I/D polymorphism at the ACE locus does not play any role in the pathogenesis and progression of migraine.

Relationship between genetic polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase as risk factors for type 2 diabetes in Tunisian patients

Background/aims The role of methylenetetrahydrofolate reductase (MTHFR) and angiotensin-converting enzyme (ACE) gene polymorphisms as being risk factors for diabetes is still controversial. The aim was to investigate the distribution of ACE and MTHFR genotypes as well as to evaluate the role of plasmatic total homocysteine levels (tHcy) and ACE activity in Tunisian patients with type 2 diabetes mellitus (T2DM). Design and methods 115 T2DM patients compared to 116 healthy volunteers. Results The ACE I/D polymorphism was significantly associated with diabetes ( p < 0.0001). The DD genotype and D allele were more frequent in patients compared to control group [DD: OR = 4.93; p < 0.0001; 95 % CI: 2.71–8.97; D: OR = 3.08, 95% CI: 2.09–4.51 p < 0.0001]. MTHFR allele and genotype frequencies did not differ between patients and controls. The susceptibility to diabetes in individuals with genotypes DD +vTT was 13.39 and in the individuals with DD + CT was 6.57 times that of the controls. However, individuals with genotypes ID + CC or II + CT have a protective effect against diabetes. The DD and TT genotypes were associated with significantly higher ACE activity and tHcy levels in diabetics. Conclusion Our data suggest that ACE ID polymorphism may act synergistically with MTHFR C677T polymorphism to assess diabetes risk.