Angiotensin-converting Enzyme DD Genotype Research Articles

Genetic Contributions to Childhood Obesity: Association of Candidate Gene Polymorphisms and Overweight/Obesity in Korean Preschool Children.

This study was aimed to investigate the association of candidate gene polymorphisms and obesity or overweight in young Korean children. A total of 190 Korean preschool children (96 control, 48 overweight, and 46 obese children) were genotyped for the angiotensin converting enzyme (ACE) insertion (I)/deletion (D), angiotensin II type 2 receptor (AT2) C3123A, transforming growth factor (TGF)-β1 T869C, vascular endothelial growth factor (VEGF) T460C, and tumor necrosis factor (TNF)-α G308A polymorphisms. No differences were found among the groups with respect to age, sex, birth weight, blood pressure levels, and serum concentrations of glucose and total cholesterol. Obese children showed a higher incidence of ACE DD genotype and D allelic frequency compared to the controls (odds ratio [OR], 2.7, 95% confidence interval [CI], 1.01–7.21; OR, 2.5, 95% CI, 1.49–4.19; all P < 0.05). The frequency of TC genotype and C allele in the TGF-β1 T869C polymorphism (OR, 2.08, 95% CI, 1.01–4.27; OR, 1.93, 95% CI, 1.15–3.21) and that in the VEGF T460C polymorphism (OR, 2.5, 95% CI, 1.19–5.28; OR, 2.15, 95% CI, 1.26–3.68) was also higher in obese children than in control subjects (all P < 0.05). Overweight children exhibited a higher frequency of the A allele in the AT2 C3123A polymorphism compared to the controls (OR, 1.72, 95% CI, 1.03–2.88, P < 0.05). There were no differences in the TNF-α G308A polymorphism among the groups. The ACE I/D, AT2 C3123A, TGF-β1 T869C, and VEGF T460C polymorphisms can affect susceptibility to obesity or overweight in Korean children.

Association of seven renin angiotensin system gene polymorphisms with restenosis in patients following coronary stenting.

Background and objective:Percutaneous coronary intervention, despite being effective for coronary revascularization, causes in-stent restenosis due to neointimal hyperplasia in a large number of patients. The renin-angiotensin system is involved in neointimal hyperplasia. This study sought to evaluate seven gene polymorphisms of key renin-angiotensin system components, including angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1a receptors, and their associations with in-stent restenosis in patients with coronary artery disease following coronary stenting.Methods and results:Three hundred and fifty-two patients undergoing coronary drug-eluting stent implantation were recruited. Seventy-five patients (21.3%) were diagnosed as restenosis by angiography. Genotyping for angiotensin-converting enzyme insertion/deletion demonstrated a significant association of angiotensin-converting enzyme DD genotype with the occurrence of restenosis. Direct DNA sequencing revealed no association of angiotensinogen (M235T, G217A, G152A, G-6A, and A-20C) or angiotensin II type I receptor A1166C polymorphisms with in-stent restenosis. However, angiotensin II type 1a A1166C polymorphism was significantly associated with increased susceptibility to restenosis in a subgroup of patients aged more than 60 years.Conclusion:Thus, our study suggests that genetic polymorphisms of angiotensin-converting enzyme insertion/deletion are associated with in-stent restenosis in coronary artery disease patients following coronary stenting.

INFLUENCE OF ANGIOTENSIN CONVERTING ENZYME GENE POLYMORPHISM ON PREGNANCY OUTCOME IN WOMEN WITH HISTORY OF PRE-ECLAMPSIA

Background: Women who have had pre-eclampsia (PE) are more prone to recurrent negative pregnancy outcomes and altered utero-placental and umbilical flows in their future pregnancy. In addition, to an increased risk of later cardiovascular diseases, which clearly suggest a shared aetiology. Yet, the mechanisms involved have not been identified. Although, the causes of PE are not well understood, there is a possibility that PE has, at least in part, a genetic basis. The physiological remodelling of spiral arteries throughout pregnancy is mediated by the rennin-angiotensin system (RAS). The ACE I/D polymorphism of the ACE gene accounted for 47% of total phenotypic variance of the serum Angiotensin converting enzyme (ACE), contributing much to the variability of the ACE level. Previous studies failed to reproduce a persistent link of ACE I/D genotype and PE in nulliparous women. Objective: In this prospective study, we analysed the association of the ACE genotype and the recurrence of PE and/or fetal growth restriction (FGR) in subsequent pregnancy in women at high risk for a previous PE as primipara, without other known risk conditions. Patients and Methods: Sixty women with history of PE as primipara, with no known risk factors apart from nulliparity, were recruited in their second pregnancy. Their ACE genotyping were detected. Uterine arteries resistance indices (RI) and umbilical artery pulsatility index (PI), were recorded at 16th, 20th, 24th weeks of gestation and clinical pregnancy outcome was analyzed, as well. Results: ACE I/D genotype distribution among our cases of 90 Egyptian pregnant women were compatible to other races in literature. DD genotype was detected in 41.1% of our cases, 34.4% were ID genotype and 24.4% were II genotype. Significant difference in ACE I/D genotype and D-allele frequency were observed in cases with recurrent PE and/or FGR. Mid trimester uterine arteries resistance indices (RI) at 16th, 20th, 24th weeks of gestation, and umbilical artery pulsatility index (PI) at 20th, 24th weeks were significantly higher in DD genotype group compared to ID and II genotype respectively. In addition, DD genotype group had significantly lower gestational age at time of delivery, lower birth weight and placental weight. Conclusion: ACE DD genotype and D- allele frequency adversely affected pregnancy outcome and utero-placental and umbilical flow velocimetry in women with history of preeclampsia as nulliparous without known risk factors apart from nulliparity.

Association between angiotensin converting enzyme gene insertion/deletion polymorphism and renal scar risk in children vesicoureteral reflex: a reappraise meta-analysis.

Vesicoureteral reflex(VUR) is a common disease in children. Some studies indicated that the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism associated with the renal scar in VUR, but not all researchers agreed with it. To clarify the effect of ACE I/D polymorphism on renal scar risk in children with VUR, we performed the present meta-analysis. PubMed, CNKI, CBM, and Embase databases were searched for studies that examined the relationship between ACE I/D polymorphism and renal scar risk in children with VUR. The Stata 12.0 software was used for statistical analyses. 11 case-control studies with 1,032 VUR patients were analyzed. The results showed that the DD genotype and D allele were associated with renal scar risk in overall VUR patients, DD vs. DI + II: OR = 1.61, 95% CI = 1.04–2.49, P = 0.03; DD vs. II: OR = 1.78, 95% CI = 1.20–2.65, P < 0.01; D vs. I: OR = 1.38, 95% CI = 1.02–1.86, P = 0.04. Similar results were revealed in Turks, but not in Caucasians and Asians. Our meta-analysis indicated that the ACE DD genotype may increase the risk of renal scar in children with VUR.

The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Associates with Habitual Physical Activity among European-American Adults

PURPOSE: The angiotensin converting enzyme (ACE) insertion (I) deletion (D) polymorphism (ACE DIP) (rs4340) is a 287 base pair sequence within intron 16 of chromosome 17q23 that accounts for half of the variation in plasma ACE levels. Due to its influence on cardiovascular and renal function, the ACE DIP has been examined for its association with sport performance. The literature regarding associations with habitual physical activity is limited and inconsistent. We examined associations of the ACE DIP and physical activity among 461 European-American adults. METHODS: 203 men and 258 women with a body mass index (BMI) of 24.3±4.8 kg·m2 completed the Paffenbarger Physical Activity Questionnaire to determine weekly walking distance. ACE II (n=119), ID (n=213), and DD (n=129) genotypes were determined using TaqMan allele discrimination assays. Multivariate analysis of covariance (MANCOVA) determined logtransformed differences among ACE DIP genotypes and weekly walking distance with gender as a fixed factor and age and BMI as covariates. Because a significant ACE DIPxBMI interaction was found (p=0.03), we categorized the sample into normal weight (NW:BMI≤24.9 kg·m2) and overweight (OW:BMI>24.9 kg·m2). We repeated the MANCOVA with gender and BMI groups as fixed factors and age as a covariate. Bonferroni corrections were used to control for multiple comparison testing with alpha levels at p<.05. RESULTS: For NW (BMI=21.7±1.8 kg·m2), participants with the ACE II reported walking 1.4±1.0 mi/wk, ID 1.2±0.9 mi/wk, and DD 1.6±1.2 mi/wk, with ID walking less than II and DD (p<0.05). For OW (BMI=29.6±4.4 kg·m2), participants with the ACE II reported walking 1.5±1.1 mi/wk, ID 1.2±1.0 mi/wk, and DD 0.6±0.8 mi/wk, with DD walking less than II (p=0.02). For NW vs OW, weekly walking distance was 1.0±2.2 mi/wk less among OW with the ACE DD genotype than NW with this genotype (p=0.02); there were no other genotype-physical activity differences within or between NW and OW (p>0.05). CONCLUSIONS: BMI interacted with ACE DD to modulate habitual physical activity levels such that weekly walking distance was ~1.0 mi/wk greater among NW than OW with ACE DD. Our findings may provide insight into the discrepancies of this literature, and have public health significance equating to a body weight differential of ~1.4 lb/yr.

Significant correlation of angiotensin converting enzyme and glycoprotein IIIa genes polymorphisms with unexplained recurrent pregnancy loss in north of Iran

Spontaneous abortion is considered as the most complex problem during pregnancy. Thrombophilia is resumed as a cause of recurrent pregnancy loss (RPL). Glycoprotein IIIa (GPIIIa) gene is involved in thrombosis and abortion. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II and is involved in thrombosis. The most common polymorphism in this gene is the insertion/deletion (I/D). In this study, we analyzed the association between ACE I/D and GPIIIa c.98C >T polymorphisms in women with unexplained RPL from the north of Iran. Sample population consisted of 100 women with unexplained RPL and 100 controls. The ACE I/D and GPIIIa c.98C>T polymorphisms were genotyped by TETRA-ARMS PCR. The association between genotypes frequency and RPL were analyzed using χ(2) and exact fisher tests. Associated risk with double genotype combinations was also investigated by binary logistic regression. There was significant association between ACE DD genotype and RPL (OR=2.04; 95% CI=0.94-4.44; p=0.036). ACE D Allele was also significantly associated with the RPL (OR=1.59; 95% CI=1.05-2.41; p=0.013). No significant association was observed between GPIIIa c.98C>T polymorphism and RPL. ACE I/D polymorphism may probably be a prognostic factor in female family members of women with the history of recurrent abortion.

Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study.

BackgroundAutism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism.MethodsConsidering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR–restriction fragment length polymorphism (PCR–RFLP) methods.ResultsThere were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64–5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37–3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26–2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008).ConclusionOur data suggests the involvement of RAS genetic diversity in increasing the risk of autism.

ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism

The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor's protection of the lungs in HF during acute fluid overload. 100 HF patients (left ventricular ejection fraction ≤40%) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500cc saline. ACE I/D genotype prevalence was: DD=28, ID =55 and II=17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco -2.3±1.3 vs. -0.8±1.9 and -0.6±1mL/mmHg/min, p<0.0001 and p<0.01; Dm -7±5 vs. -3.2±7.4 and -1.3±5mL/mmHg/min, p<0.05, respectively) and a higher increase in VE/VCO2 slope than II (1.8±1.9 vs. -0.8±2.3, p=0.01). ACE DD genotype is associated with higher vulnerability of the alveolar-capillary membrane to acute fluid overload in HF patients treated with ACE inhibitors.

ASSOCIATION OF MTHFR (C677T) AND ACE (I/D) POLYMORPHISMS WITH HYPERTENSION AND RESPONSE TO TREATMENT AMONG EGYPTIAN PATIENTS

Hypertension, a well-known epidemic health disease, is risk factor for various cardiovascular, peripheral vascular and renal diseases. Renin angiotensin system (RAS) being the most important pathogenic mechanism of hypertension is mediated by a key component; the angiotensin converting enzyme (ACE). Moreover, Mutations in the methylenetetrahydrofolate reductase gene (MTHFR) have been established to be associated with the risk of cardiovascular disease as well as hypertension. This case-control study was conducted out to investigate the potential relationship of ACE (I/D) and MTHFR (C677T) gene polymorphisms with hypertension susceptibility and the responsive ability of antihypertensive drugs in Egyptian hypertensive patients. Thirty six patients suffering of high blood pressure were compared with age and sex matching 14 control cases. MTHFR (C677T) and ACE (I/D) polymorphisms were genotyped by polymerase chain reaction (PCR). The demographic and clinical features of patients and control showed no particular significance (p > 0.05) except for the consanguinity and the obesity. For MTHFR polymorphism frequency, total hypertensive cases showed significantly higher frequency rate for the mutant allele 677T compared to controls with a lower frequency of the wild type 677CC genotype. Whereas the mutant 677TC+TT genotypes were not significantly associated with the hypertension risk when compared to the wild genotype among the case group. For ACE gene polymorphism, also showed only higher frequency rates of DD allele. Interestingly, ACE DD genotype showed significant association with blood pressure, obesity and diabetes. Finally in response of the antihypertensive drugs, we found that, the best responsive group is DD genotype group when treated with the ACE inhibitors. These result suggested that the MTHFR polymorphism was not associated with hypertension while the ACE DD genotype may be associated with essential hypertension and considered as a potent risk factor for hypertension and moreover it is the best responsive group when treated with ACE inhibitors in Egyptian patients.

The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with adaptation to high altitude: A meta-analysis.

Background:Fluid retention is linked to the physiology and pathophysiology of humans at high altitude (HA). The angiotensin-converting enzyme (ACE) gene plays a role in the regulation of plasma volume and vascular tone.Materials and methods:In this meta-analysis, eligible studies published before 1 September 2015 that focused on the association between the ACE insertion/deletion (I/D) polymorphism and HA adaption were identified by searching the PubMed, Web of Science, Embase and Medline online databases. We used a fixed-effects model and assessed the study qualities multiple times.Results:The seven selected studies included a total of 582 HA-native individuals and 497 low-altitude controls, and these subjects were analyzed for the ACE I/D gene polymorphism. A significant association was found between the ACE DD genotype and HA maladaptation. The results for genotype DD versus ID + II were as follows: Odds ratio (OR) = 0.46; 95% CI 0.31–0.70; p = 0.0002. The results for genotype ID versus DD were as follows: OR = 1.97; 95% CI 1.27–3.06; p = 0.002.Conclusions:Our findings suggested that the DD genotype of ACE is a risk factor for HA maladaptation and that the presence of fewer ACE DD allele carriers in a population indicates a greater ability of that population to adapt to HA.

Association of GSTM1, GSTT1, GSTP1-ILE105VAL and ACE I/D polymorphisms with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin. The aim of this study is to clarify the relationships between susceptibility and severity of AS and GST-mu1 (GSTM1), GST-theta1 (GSTT1), GST-pi1 (GSTP1)-Ile105Val and angiotensin-converting enzyme (ACE) I/D polymorphisms in AS patients. One hundred thirty-eight AS patients and seventy-one healthy controls were enrolled in this study. Erythrocyte sedimentation rate and C-reactive protein (CRP) levels of the AS patients were recorded. The scores of the numeric rating scale (NRS) pain, the Bath Ankylosing Spondylitis Activity Index, the Bath Ankylosing Spondylitis Metrology Index and the Bath Ankylosing Spondylitis Functional Index were calculated. The genotypes distributions and allele frequencies of GSTM1, GSTT1, GSTP1-Ile105Val and ACE I/D polymorphisms were compared between patients and healthy controls. The Multiplex polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism methods were used to detect the polymorphisms of ACE I/D, the GSTT1 and GSTM1 genes and the GSTP1-Ile105Val polymorphism, respectively. There were significantly higher levels of the GSTT1 null and the ACE II genotypes in AS patients compared to those in healthy controls (p = 0.002 and 0.005, respectively). We found significantly higher levels of CRP and the NRS pain scores in the patients with ACE ID or DD genotypes compared to those in the patients with ACE II genotypes (p = 0.005 and 0.035, respectively). The present results showed that genes involved in protection from oxidative stress and ACE gene may influence disease development and course in AS.

PS-208 Genetic Predisposition To The Development Of Bronchopulmonary Dysplasia In Infants Born Prematurely

<h3>Background and aims</h3> Bronchopulmonary dysplasia (BPD) is an unfortunately common outcome following premature birth. Genetic factors influence BPD development but their role is part of a complex interaction with environmental factors. We postulated that alterations in the gene as well as imbalances in gene products may affect BPD development. <h3>Methods</h3> The NIH human genome database was interrogated for previously identified gene polymorphisms that have been associated with neonatal respiratory conditions. Angiotensin converting enzyme (ACE) and surfactant proteins A-D gene candidates were selected based upon clinical plausibility for the study population. DNA was extracted from whole blood and Guthrie card specimens. Surfactant single nucleotide polymorphism (SNP) genotyping was arranged using the Taqman technique. ACE gene primers were obtained for the previously known insertion/deletion polymorphism and PCR analysis was performed. <h3>Results</h3> 236 infants born prematurely survived to 28 days postnatal age and contributed to genotype analysis. 106 infants did not develop BPD and 130 infants did develop BPD (54 mild, 29 moderate, 47 severe). Both gestational age and birth weight were significantly different between those infants who did and did not develop BPD and predicted BPD development with an area under the ROC of 0.88 and 0.82 respectively. We demonstrated using multifactorial statistical analysis that the inclusion of the ACE genotype to a predictive statistical model of BPD development improves the predictive potential of the model (area under ROC curve 0.88). <h3>Conclusion</h3> The presence of the ACE DD genotype is associated with a higher likelihood of developing BPD.

Angiotensin-converting enzyme insertion/deletion gene polymorphisms is associated with risk of glioma in a Chinese population.

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has recently been linked to the pathogenesis and progression of human cancers. The aim of this study was to evaluate the potential association between ACE I/D polymorphism and glioma in a Chinese population. A case-control study involving patients with 800 glioma and 800 controls was conducted. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the ACE I/D genotypes. Glioma cases had a significantly higher frequency of DD genotype [odds ratio (OR) = 1.61, 95% confidence interval (CI) = 1.12, 2.32; p = 0.01] than controls. When stratified by the grade of glioma, cases with WHO IV glioma had a significantly higher frequency of DD genotype (OR = 1.51, 95% CI = 1.03, 2.21; p = 0.03). When stratified by the histology of glioma, there was no significant difference in the distribution of each genotype. Our study suggested that the ACE DD genotype was associated with a higher glioma risk in this Chinese population. To the best of our knowledge, this is the first report describing the potential association between ACE I/D polymorphism and glioma. Additional studies are needed to confirm this finding.

ASSOCIATION OF ANGIOTENSIN CONVERTING ENZYME GENE POLYMORPHISM AND DIABETIC NEPHROPATHY IN TYPE 2 DIABETES MELLITUS IN SHARKIA GOVERNORATE

Diabetic nephropathy (DN) is the leading cause of end – stage renal disease (ESRD) worldwide. The pathogenesis of this condition is not well understood clearly at present. The relationship between angiotensin- converting enzyme (ACE) insertion/ deletion (I/D) gene polymorphism and risk of DN is still conflicting. Therefore, we designed this study to investigate the association of ACE I/D gene polymorphism and development of diabetic nephropathy in a cohort of Egyptian population from Sharkia Governorate. Ninety patients with type 2 diabetes mellitus were included in the study. The first group included 45 without nephropathy while the second group included 45 with nephropathy. Both groups were subjected to full history taking, physical examination, routine laboratory investigations including fasting and 2 hours post prandial blood glucose, glycosylated hemoglobin, urine albumin excretion and urinary creatinine estimation. ACE I /D genotyping was carried out by polymerase chain reaction (PCR) amplification using allele specific primers. The frequencies of ACE DD, ID and II genotypes in group I were 11.1%, 55.6%, 33.3%. But in group II were 33.3%, 46.7%, 20% respectively. DD genotype was significantly more frequent in group II than group I (33.3% VI 11.1%), odd ratio1.5; 95%, Confidence interval (1.049-2.145), p<0.01). The ACE DD genotype is associated with diabetic nephropathy in Sharkia governorate.

POOR PROGNOSIS PREDICTOR IN ISCHEMIC HEART DISEASE PATIENTS WITH CONFIRMED HEMODYNAMICALLY SIGNIFICANT CORONARY ARTERY ATHEROSCLEROSIS IN THE DYNAMICS OF LONG OBSERVATION

The purpose of the study - to determine the clinical-anamnestic, instrumental parameters, and genetic factors, that that determine the development of adverse cardiovascular events (ACVE) in patients with ischemic heart disease (IHD) with a verified hemodynamically significant coronary artery (CA) atherosclerosis at long follow-up.Materials and methods. The study involved 318 patients with IHD with the presence of hemodynamically significant stenoses (stenosis&gt; 50%) at least one CA according to selective coronary angiography (SCG). Evaluation of patients included determination of the ankle-brachial index (ABI), Doppler sonography of the lower extremities vessels (LEV) and carotid artery (CARA) with a quantitative assessment of the intima-media thickness (IMT), carrying a load test by the modified Bruce protocol and determination of glomerular filtration rate (GFR) by MDRD. The observation period lasted (28,4 + 4,8) months. Study endpoints were cardiovascular death, myocardial infarction (MI), unstable angina, need for revascularization, and cerebrovascular accident. Study of the angiotensin converting enzyme (ACE) I/D polymorphism and endothelial NO-synthase (eNOS) gene promoter T-786S polymorphism was performed using polymerase chain reaction.Results and discussion . 82 (25.8%) patients in whom the study endpoints occurred were included in group I, 236 patients without ACVE - group II. According to odds ratios (OR) chance of developing ACVE in the examined patients was increased in the presence of hypertension (AH) (OR = 2,06, 95 % CI [1,05-3,84], p &lt;0,05), diabetes mellitus (DM), type 2 (OR = 2,12, 95 % CI [1,15-3,92], p &lt;0,05), abdominal obesity (OR = 1,82, 95 % CI [1,10-3,01], p &lt;0,05), smoking (OR = 2,03, 95 % CI [1,21-3,36], p &lt;0,05), family history of cardiovascular disease (CVD) early onset (OR = 1,81, 95 % CI [1,0-2,95], p &lt;0,05), more than one MI in anamnesis (OR = 2,06, 95 % CI [1,11-3,84], p &lt;0,05), reducing EF &lt; 45% ( OR = 1,77, 95 % CI [1,05-2,99], p &lt;0,05), decline in renal function (OR = 1,89, 95 % CI [1,1-3,25] p &lt; 0.05), as well as by atherosclerotic lesions of CARA (OR = 2,28, 95 % CI [1,23-4,23], p &lt;0,05) and LEV (OR = 1,93, 95 % CI [1,11-3,35], p &lt;0,05), the lesions of three CA (OR = 1,77, 95 % CI [1,06-2,94], p &lt;0,05) and diffuse type of lesion according SCG (OR = 3,56, 95 % CI [1,15-5,59], p &lt;0,05). In the I patients group frequency of mutant DD genotype of ACE gene I/D polymorphism was greater than in Group II (37,8% vs 24,6%, p &lt;0,05). The presence of DD genotype was associated with an increased likelihood of ACVE in patients with verified CA atherosclerosis (OR = 1,87, 95% CI [1,10-3,18], p = 0,03). The frequency of eNOS gene promoter T-786C polymorphism mutant CC genotype occurrence was also higher In the first patients group than in the II group (37.6% vs. 14,8%, p &lt;0,05). Chance of poor prognosis for carriers of mutant CC genotype and C allele of eNOS gene promoter T-786C polymorphism was significantly higher (OR = 3,46, 95% CI [1,37-8,48], p = 0.014).Conclusions. An adverse cardiovascular events development in patients with stable IHD with verified coronary artery (CA) atherosclerosis is associated with the presence of arterial hypertension, type 2 diabetes mellitus, smoking, family history of CVD early onset, as well as more than one MI in anamnesis, with atherosclerotic lesions of the carotid arteries and blood vessels of the lower extremities, lesions of the three CA and diffuse type of lesion according to SCG, reduced left ventricular ejection fraction less than 45% and declining of renal function according to GFR. The DD genotype of angiotensin-converting enzyme I/D polymorphism and the CC genotype of endothelial NO-synthase gene T-786S promoter polymorphism associated with poor prognosis in patients with stable IHD. The probability of adverse cardiovascular events in the presence of these polymorphic markers increases in 1.87 and 3.46 times, respectively.

Association of ACE and MTHFR genetic polymorphisms with type 2 diabetes mellitus: Susceptibility and complications

Polymorphisms of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes have been proposed to be associated with type 2 diabetes mellitus (T2DM) with conflicting results. This work was planned in order to check for the association of these polymorphisms with the susceptibility for and complications of T2DM among Egyptian cases. This is a case controlled study involving 203 patients with T2DM and 311 healthy controls. Polymorphic variants of ACE I>D and MTHFR (677 C>T and 1298 A>C) were determined using the polymerase chain reaction (PCR) restriction analysis technique. The susceptibility to T2DM was higher among subjects having the MTHFR 677TT (odds ratio (OR)=2.2, p=0.01), MTHFR 1298 AA (OR=1.84, p=0.001) and ACE (ID+II) (OR=2.0, p=0.0007) genotypes. Logistic regression analysis showed that MTHFR 677T allele was a risk factor for diabetic retinopathy (DR) (OR=3.47, p<0.001), diabetic polyneuropathy (DPN) (OR=5.2, p<0.0001) and ischemic heart disease (IHD) (OR=2.9, p<0.05), while MTHFR 1298 C allele was a risk factor for DR (OR=4.2, p<0.001) and the ACE DD genotype was a risk factor for DPN (OR=3.1, p<0.001). The MTHFR 677 TT genotype was associated with T2DM susceptibility and complications (DR, DPN and IHD). The MTHFR 1298 CC, AC and ACE DD genotypes were associated with DR and DPN.

ACE I/D Gene Polymorphism in Children with Family History of Premature Coronary Disease.

Letter to the editor regarding the article by de Albuquerque et al: Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling. I read with interest the recent review article by de Albuquerque et al1 published in the Arquivos Brasileiros de Cardiologia entitled “Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling.” They showed that the DD genotype of Angiotensin-converting enzyme (ACE) gene polymorphism was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile1. Atherosclerosis, the major cause of CAD, manifests clinically in adulthood. However, this disease begins very early in life, often during childhood. Genetic and environmental factors, gene–environment interaction effects also come into play in the development of atherosclerosis. Family history is the most significant independent risk factor for CAD. In our study, we included a total of 140 children, 72 males and 68 females between the ages of 4.9 and 15.7 years. Among these children, 73 had a parental history of premature CAD (parents have been diagnosed with the CAD by coronary angiographic study, ages below 55 for men and 65 for women) and the rest of 67 belonged to our control group (parents have shown normal coronary angiographic study). The participants were screened for the mutations ACE I/D gene polymorphisms. The genotypes of ACE I/D were significantly different between the study and control groups (p = 0.01). The frequency of D/D genotype was significantly higher in the study group than the control group (respectively, 20/73 vs. 3/67, p = 0.01) (Table 1). The frequency of the D allele was slightly higher in study group (0.52) than in control group (0.27) (p = 0.005). Table 1 The frequencies of the ACE I/D gene polymorphisms in study group and control group, and the odds ratios with 95% CI The angiotensin converting enzyme is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. The ACE insertion/deletion (I/D) polymorphism results from the absence or presence of an alu repeat located in intron 16 of the ACE gene. The D allele of an insertion/deletion (I/D) polymorphism of the gene encoding ACE is associated with higher plasma ACE concentrations2. Many studies have investigated the association between the DD genotype of ACE gene I/D polymorphic variant and CAD3,4. However, these outcomes have not been supported by the other studies5. In present study, the frequencies of D/D genotype and D allel of ACE gene considerably higher in children with parental history of premature CAD than control group. We showed that the frequencies of the DD genotype and the D allel of ACE I/D gene polymorphism are higher in children with parental history of premature CAD. This results may be associated with an increased risk for development of atherosclerosis. It may be contribute to the detection of the risk of children with a parental history of CAD. Thus, further large population studies must be done to confirm this results. The study protocol was approved by the Local Ethical Committee of Celal Bayar University, and informed written consent was obtained from all participants. This study was funded by Celal Bayar University.

ACE gene polymorphism and serum ACE level with Progression of Nephropathy in Type 2 Diabetic Patients

Background. One of the most common complications of diabetes mellitus (DM) is diabetic nephropathy (DN). Angiotensin- converting enzyme (ACE) gene was the first candidate gene of renin-angiotensin system (RAS) for predisposition to DN.Objective. Investigation whether the ACE insertion/deletion (I/D) polymorphism is associated with Egyptian type 2 diabetic patients (T2DM) with nephropathy. In addition, the study investigated the relationship between variants of ACE I/D gene polymorphism and serum ACE level and the progression of nephropathy in Egyptian T2DM patients.Methods. A total of 85 T2DM patients (45 with nephropathy and 40 without nephropathy) besides 45 healthy (non-diabetic) age-matched subjects were recruited in this study for comparison. The (I/D) polymorphism of the ACE gene was investigated using PCR and serum ACE levels were determined using ELISA.Results. The frequency of ACE DD genotype and D allele was significantly higher in DN patients when compared to control healthy subjects and diabetic patients without nephropathy. In addition our results showed a significant association between DD genotype of ACE gene and elevated serum ACE level.Conclusion. The present study showing a strong association between the D allele and/or DD homozygous of ACE gene and diabetic patients developed nephropathy. In addition, individuals with D allele have higher levels of serum ACE compared to those having I allele. ACE gene polymorphism and serum ACE level may serve as a susceptibility biomarker for nephropathy in type 2 diabetic patients.

Interaction of Genetic Risk Factors Confers Increased Risk for Metabolic Syndrome: The Role of Peroxisome Proliferator-Activated Receptor γ

The aim of the study was to estimate the influence of interactions between peroxisome proliferator-activated receptor γ (PPARγ) and target genes lipoprotein lipase (LPL), interleukin 6 (IL6), angiotensin converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) on metabolic syndrome (MetSy) and its traits. The study included 527 participants (263 with MetSy and 264 controls). Genotyping of PPARγ Pro12Ala, LPL PvuII (-/+), IL6 -174G>C, ACE I/D and AT1R 1166A>C was performed using polymerase chain reaction-restriction fragment length polymorphism-based methods. Interaction between PPARγ Pro12Ala and LPL Pvu(-/+) improved prediction of MetSy over and above prediction based on a model containing no interactions (χ(2)=7.22; df=1; p=0.007). In the group of participants with PPARγ Pro12Ala or Ala12Ala genotypes, those with the LPL Pvu (-/+) or (+/+) genotype had greater odds for MetSy (odds ratio OR=5.98; 95% confidence interval CI: 1.46-24.47, p=0.013). Interaction between PPARγ Pro12Ala and IL6 -174G>C improved prediction of high fasting blood glucose (χ(2)=13.99; df=1; p<0.001). PPARγ Ala12 variant was found protective in patients with IL6 -174GG genotype (OR=0.10; 95% CI: 0.02-0.57, p=0.01), while in the case of IL6 -174C allele carriers, for PPARγ Ala12 carriers, larger odds for high glucose levels compared with Pro12 variant were observed (OR=2.39; 95% CI: 1.11-5.17, p=0.026). Interactions of PPARγ and ACE were significant for BMI. In the group with ACE DD genotype, those with PPARγ Pro12Ala or Ala12Ala genotype have greater odds for obesity (OR=9.98; 95% CI: 1.18-84.14, p=0.034). PPARγ gene variants can, in interaction with some of its target genes, modulate physiological processes leading to the development of MetSy.

Association of angiotensin-converting enzyme and angiotensin-converting enzyme-2 gene polymorphisms with essential hypertension in the population of Odisha, India

Background: Hypertension is a serious health issue worldwide and essential hypertension, which includes 90–95% of the cases, is influenced by both genetic and environmental factors. Identification of these factors may help in control of this disease. The Insertion/Deletion (I/D) polymorphism in Angiotensin-Converting Enzyme (ACE) gene and rs2106809 (C > T) polymorphism in Angiotensin-Converting Enzyme 2 (ACE2) gene have been reported to be associated with essential hypertension in different populations.Aim: To investigate the association of ACE I/D and ACE2 rs2106809 polymorphisms with essential hypertension in the population of Odisha, an eastern Indian state.Subjects and methods: A total of 246 hypertensives (159 males and 87 females) and 274 normotensives (158 males and 116 females) were enrolled in the study. Detailed anthropometric data, tobacco, alcohol and food habits were recorded and 2 ml of venous blood was collected for biochemical and genetic analysis.Results: The DD genotype of ACE and TT genotype of ACE2 were significantly high among female hypertensives, while T allele of ACE2 was linked to male hypertensives. In the male population, alcohol was also identified as a potential risk factor.Conclusion: Among females, ACE I/D and ACE2 rs2106809 polymorphisms, while among males, ACE2 rs2106809 polymorphism and alcohol consumption are associated with essential hypertension in the study population.