ACE DD Genotype Research Articles

ACE I/D sequence variants but not MTHFR C677T, is strongly linked to malignant glioma risk and its variant DD genotype may act as a promising predictive biomarker for overall survival of glioma patients

ObjectiveACE I/D and MTHFR C677T gene polymorphisms can be seen as candidate genes for glioma on the basis of their biological functions and their involvement in different cancers. The aim of this study was to analyze potential association and overall survival between MTHFR C677T and ACE I/D polymorphism in glioma patients in our population. Materials and methodsWe tested genotype distribution of 112 glioma patients against 141 cancer-free controls from the same region. Kaplan-Meier survival analysis was performed to evaluate overall survival of patients for both genes. ResultsNo significant differences were found among MTHFR C677T wild type C and variant genotypes CT/TT with glioma patients. In ACE, the distribution of variant ID and DD was found to be significantly higher in glioma cases as compared to controls (p<0.0001). ACE DD genotypes were highly presented in glioma cases 26.8% versus 10.6% in controls (p<0.0001) and conferred 5-fold risk for predisposition in glioma cases. Per copy D allele frequency was found higher in cases than in controls (0.54 versus 0.25: p<0.0001). Interestingly we found a significant overall survival (with log rank p<0.01) in patients who presented with ACE DD genotypes had the least estimated overall survival of 13.4months in comparison to 21. 7 and 17.6months for ACE II and I/D genotypes respectively. ConclusionWe conclude ACE I/D polymorphism plays a vital role in predisposition of higher risk for glioma. We also suggest that ACE DD genotypes may act as an important predictive biomarker for overall survival of glioma patients.

Association of the genetic and traditional risk factors of ischaemic heart disease with STEMI and NSTEMI development.

Introduction:To evaluate the influence of traditional risk factors of ischaemic heart disease and genetic factors to predict different types of acute coronary syndromes.Materials and methods:Five hundred and twenty-three patients with acute coronary syndromes (393 with ST elevation myocardial infarction (STEMI) and 130 with non-ST elevation myocardial infarction (NSTEMI)) comprised the study group. The control group consisted of 645 subjects free from symptoms of ischaemic heart disease and stroke. Genetic polymorphisms of MMP-2 (–735) C/T, MMP-2 (–1306) C/T, MMP-3 (–1171) 5A/6A, MMP-9 (–1562) C/T and ACE I/D were evaluated using polymerase chain reaction.Results:Patients with acute coronary syndromes more often had ID or II genotype than DD genotype of ACE (P = 0.04) and 5A5A or 5A6A genotype than 6A6A genotype of MMP-3 (P = 0.02) in comparison to the control group. The genotypes of other matrix metalloproteinase genes did not differ between the groups. 5A5A and 5A6A genotypes of MMP-3 (odds ratio (OR) 1.5; P = 0.021), II and ID genotypes of ACE (OR 1.7; P = 0.006) along with traditional ischaemic heart disease risk factors such as smoking (OR 4.9; P = 0.001), hypertension (OR 2.0; P = 0.001), diabetes mellitus (OR 2.9; P = 0.001) and dyslipidaemia (OR 2.1; P = 0.001) increased the risk of STEMI. However, the polymorphism of MMP-3 5A/6A and ACE I/D was not associated with the occurrence of NSTEMI.Conclusions:Genetic polymorphisms of MMP-3 5A/6A and ACE I/D along with conventional ischaemic heart disease risk factors increase the risk of the occurrence of STEMI, while having no influence on the pathogenesis of NSTEMI.

The Combined Effect of ACE, TCF7L2, and PPARGC1A Gene Polymorphisms in Diabetic Nephropathy

Objective: This study was performed for investigation the relationship between variants of ACE, TCF7L2 and PPARGC1A gene polymorphisms individually or in combination with the development of nephropathy in T2DM. Subject and Methods: The study was included 85 T2DM patients (45 with nephropathy and 40 without nephropathy), and 45 healthy control subjects. The I/D polymorphism of ACE gene was evaluated by PCR method. The polymorphisms rs7903146 (C/T) of TCF7L2 gene and Gly482Ser (G/A) and Thr394Thr (G/A) of PPARGC1A gene were evaluated by PCR-RFLP analysis. Results: The frequency of ACE DD genotype and D allele was significantly higher in DN patients when compared to diabetic without nephropathy. The frequency of TCF7L2 rs7903146 TT genotype and T allele were significantly associated with DN patients compared to T2DM. Moreover, a significant association in A allelic frequencies was observed in DN cases compared to T2DM patients without nephropathy. No differences in the genotypic and allelic frequencies between T2DM patients with and without nephropathy were found for the Thr394Thr polymorphism. Conclusions: Our study suggested that candidate gene polymorphisms I/D of ACE, rs7903146 of TCF7L2 and Gly482Ser of PPARGC1A individually or in combination may act as susceptibility biomarkers for nephropathy in T2DM.

Synergistic effect of ACE and AGT genes in coronary artery disease

Polymorphisms of the renin-angiotensin system genes influence the pathogenesis of atherosclerosis and are connected with heart diseases. We explore the potential associations of ACE (I/D) and AGT (M235T) gene polymorphisms with coronary artery disease (CAD). A total of one hundred and twenty Egyptian patients (Sixty with CAD and sixty without CAD) and fifty healthy control subjects were included in the study. Genotyping of ACE (I/D) and AGT (M235T) were analyzed by the polymerase chain reaction (PCR) technique. Serum lipid profiles (total cholesterol, triglyceride, HDL-C) were measured by the enzymatic colorimetric method. Our data showed that the ACE D allele frequency (P<0.0001; odds ratio [OR]=2.538, 95% confidence interval [CI]=1.468–4.388), DD genotype (P<0.0001, OR=0.239, 95% CI=0.066–0.866), the frequency of AGT T allele (P<0.0001, OR=2.915, 95% CI=1.666–5.097) and TT genotype (P<0001, OR=0.316, 95% CI=0.078–1.280) were significantly more prevalent among CAD patients and may be predisposing to CAD. We further found that the concomitant presence of the ACE-DD and AGT-TT genotypes increased the risk of CAD (P=0.017, OR=0.120, 95% CI=0.042–0.347). This study demonstrated the contribution of ACE (I/D) and AGT (M235T) gene polymorphisms individually or in combination to the presence of CAD risk in the Egyptian population. The ACE D allele and AGT T allele may be predictive in individuals at risk of developing CAD.

Genetic determinants of hypertension in two national cohorts of Mountain Shoria

To estimate the prevalence of the genotypes of the candidate genes ACE (I/D, rs4646994), ADRB1 (Ser49Gly, A/G, rs1801252) ADRA2B (I/D), MTHFR (C677T, Ala222Val, rs1801133), and eNOS (4b/4a) and their association with hypertension in two ethnic groups of Mountain Shoria. A clinical and epidemiological study was conducted in a population compactly living in the hard-to-reach areas of Mountain Shoria (the settlements of Orton, Ust-Kabyrza, and Sheregesh of the Kemerovo Region). A continuous method was used to survey 1178 residents from the above settlements; the sample consisted of adults (aged 18 years and older), 565 people were genotyped. The prevalence of hypertension among the population of Mountain Shoria was 42.3%. The incidence of this disease among the Shorians was lower (39.9%) than that among the representatives of non-indigenous people (46.1%). The ethnically justified peculiarities of the association of ADRA2B and ACE I/D polymorphisms with hypertension were established. There were fewer patients with hypertension among ACE ID and ADRA2B DD genotype carriers in the cohort of the Shorians than in that of the non-indigenous population: 40.6% versus 58.6% and 38.3% versus 64%, respectively. Conversely, there were more hypertensive patients among the carriers of the homozygous ACE DD genotype in the native ethnic group (60%) than in the non-indigenous one (37.1%). Adverse prognostic ACE DD, ADRB1 AA, MTHFR TT, and eNOS 4a/4a genotypes were more frequently observed in the non-indigenous ethnic groups; the ADRA2B DD genotype was more common in the native population. Hypertension was associated with the ACE DD, МTHFR CT, and ADRB1 AA genotypes in the native ethnic group and with the ACE ID genotype in the non-indigenous population.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and interferon-β treatment response in multiple sclerosis patients: a preliminary report.

We investigated the effect of the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to interferon-β (IFN-β) therapy in Croatian and Slovenian patients with multiple sclerosis (MS). A total of 275 IFN-β treated MS patients [162 responders (Rs) and 113 nonresponders (NRs)] were genotyped by PCR. The ACE I/D genotype distribution and allele frequencies did not differ between female Rs and NRs. However, male NRs tended to have a greater prevalence of the DD genotype (P=0.073; odds ratio: 2.64; 95% confidence interval: 0.91-7.60) and a significantly higher frequency of the D allele (P=0.022; odds ratio: 2.43; 95% confidence interval: 1.13-5.20) than male Rs. Multiple forward stepwise regression analysis indicated that the negative response to IFN-β therapy was associated with the ACE-DD genotype in men (β=0.371; multiple R change: 0.132; P=0.009) and a higher pretreatment relapse rate in both men (β=-0.438; multiple R change: 0.135; P=0.015) and women (β=-0.208; multiple R change: 0.042; P=0.034). The ACE I/D polymorphism and pretreatment relapse rate accounted for ∼26.7% of the IFN-β response variability among the men in the sample. Further studies of a larger number of MS patients from different populations are necessary to evaluate these preliminary findings.

The influence of genetic polymorphisms on performance and cardiac and hemodynamic parameters among Brazilian soccer players.

This study investigated whether ACTN3 R577X, AMPD1 C34T, I/D ACE, and M235T AGT polymorphisms can affect performance tests such as jumping, sprinting, and endurance in 220 young male athletes from professional minor league soccer team from São Paulo Futebol Clube, Brazil. I/D ACE and M235T AGT polymorphisms were also analyzed according to cardiac and hemodynamic parameters. Athletes were grouped or not by age. DNA from saliva and Taqman assays were used for genotyping 220 athletes and the results were associated with performance tests. Ventricle mass, ventricle end-diastolic diameter, end-diastolic volume, and ejection fraction were assessed by echocardiogram. Arterial pressure, heart rate, and oximetry were assessed by a cardioscope. The main results of this study were that athletes who carried RR/RX (ACTN3) and DD (ACE) genotypes presented better performance during jump and sprint tests. On the other hand, athletes with ID/II genotype presented better results during endurance test, while AGT genotypes did not seem to favor the athletes during the evaluated physical tests. CC genotype (AMPD1) only favored the athletes during 10-m sprint test. Although there are environmental interactions influencing performance, the present results suggest that RR/RX ACTN3 and ACE DD genotypes may benefit athletes in activities that require strength and speed, while II ACE genotype may benefit athletes in endurance activities. This information could help coaches to plan the training session to improve the athletes' performance.

Angiotensin converting enzyme gene (I/D) polymorphism and susceptibility of childhood asthma and coincident atopic diseases

ACE level has been linked to bronchial hyper-reactivity and airway inflammation. ACE gene (I/D) polymorphism has been associated with asthma and atopy although the findings between cohorts have not been uniform.We conducted this cross-sectional study to evaluate the possible role of ACE gene I/D polymorphism in the association between bronchial asthma and other atopic diseases in asthmatic children and adolescents.Genotyping of ACE gene (I/D) polymorphism was done by RFLP-PCR in 200 asthmatic children and adolescents. Serum levels of total IgE were measured by ELISA. Skin prick test was performed on all participants.We found a high frequency of DD genotype compared to other genotypes. We also noticed that children carrying ACE DD genotype had a higher incidence of asthma and a higher coincidence of allergic rhinitis.In conclusion, our findings represent an evidence for the role of ACE gene I/D polymorphism in childhood asthma and its coincidence with allergic rhinitis.

Ethnogenetic aspects of obesity and disorders of carbohydrate metabolism as a risk factor of arterial hypertension

Objective - to explore the association of candidate genes of arterial hypertension ACE, ADRA2B, ADRB1, MTHFR and eNOS with obesity and impaired glucose metabolism based on ethnicity. Materials and methods. Clinical and epidemiological study of compactly living population in the remote areas of the Mountain Shoria (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of these settlements were surveyed with the help of continuous sampling method; the sample consisted of adults (18 years and older). Results. In the group of respondents of the indigenous nationality averages Quetelet index, waist circumference and fasting blood glucose, depending on the polymorphism of candidate genes of arterial hypertension ACE, ADRA2B, ADRB1, MTHFR and eNOS were lower than in non-indigenous ethnic group surveyed. In a population of Shor was found a statistically significant relationship with the body mass index of ACE gene genotypes in a population of non-indigenous representatives - with genotypes of ADRA2B gene. In the group of indigenous ethnic group revealed the relationship from ACE gene polymorphism. Regardless of nationality, found associative connection of the indicator polymorphism of ADRA2B gene. The level of plasma glucose levels in a population of non-indigenous ethnic group was correlated with genotypes of ADRA2B gene. Conclusion. Metabolic abnormalities were detected less frequently in indigenous ethnic group compared with the non-indigenous. In Shor group ACE DD genotype and ADRA2B genes associated with obesity, the genotype 4a/4a eNOS gene - with abdominal obesity. In the group of non-indigenous ethnic group CC genotype of the MTHFR gene was associated with abdominal obesity, II genotype of ACE gene and DD ADRA2B gene - with impaired carbohydrate metabolism.

ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study.

BackgroundTo date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. Aim: To examine the association between these variants and sprint time in elite athletes.MethodsWe collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants.ResultsOn average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively.ConclusionsDespite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2462-3) contains supplementary material, which is available to authorized users.

Does angiotensin-converting enzyme-1 (ACE-1) gene polymorphism lead to chronic kidney disease among hypertensive patients?

Background: Hypertension is one of the important contributing factors linked with both causation and development of kidney disease. It is a multifactorial, polygenic, and complex disorder due to interaction of several risk genes with environmental factors. The present study was aimed to explore genetic polymorphism in ACE-1 gene as a risk factor for CKD among hypertensive patients. Methods: Three hundred patients were enrolled in the study. Ninety were hypertensive patients with CKD taken as cases, whereas 210 hypertensive patients without CKD were taken as controls. Demographic data including age, sex, Body mass index (BMI), and other risk factors were also recorded. DNA was extracted from blood by salting out method. Genotyping of ACE gene was done by PCR technique. All the statistical analysis was done by using Epi Info and SPSS version 16 software (SPSS Inc., Chicago, IL). Results: Mean age was higher in the control group (p < 0.05). Variables among two groups were compared out of which age, BMI, hemoglobin (Hb) was found to be statistically significant whereas other variables like systolic blood pressure, triglyceride and low-density lipoprotein were not. Blood urea and serum creatinine levels were statistically significant in the two genotypes (p < 0.05). Total and HDL cholesterol were statistically significant for DD genotype of ACE gene (OR = 1.42, 95% CI = 0.72–2.81). Similarly, the risk for CKD among hypertensive patients was also associated with D allele of ACE gene (OR = 1.25, 95% CI = 0.86–1.79). Conclusion: It is concluded that ACE-DD genotype may be a risk factor for the causation and development of chronic kidney failure among hypertensive patients.

Association of serum levels of AngII, KLK1, and ACE/KLK1 polymorphisms with acute myocardial infarction induced by coronary artery stenosis.

Introduction:The study aims to confirm the association of acute myocardial infarction (AMI) with serum angiotensin II (AngII), kallikrein1 (KLK1), and ACE/KLK1 polymorphisms.Materials and methods:Serum AngII/KLK1 levels and ACE and KLK1 genotypes were determined in 208 patients with AMI and 216 normal controls. Binary logistic regression was used for data analysis.Results:The differences in serum AngII levels were statistically significant between the groups. After adjusting for potential confounding factors, high serum levels of AngII and KLK1 significantly increased the risk of AMI. The individuals with ACE DD and KLK1 GG genotypes significantly increased the risk of AMI compared with those harboring the ACE II and KLK1 AA genotypes (OR = 8.77, 95% CI = 1.74–44.16).Conclusions:(1) Increasing the serum levels of AngII increased the risk of AMI. (2) The risk of AMI increased significantly when the serum levels of AngII and KLK1 simultaneously increased. (3) Individuals with the combined genotypes of ACE DD and KLK1 GG showed significantly increased risk of AMI compared with those with the combined genotypes of ACE II and KLK1 AA.

The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism.

ObjectiveA silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle.MethodsFifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc.ResultsCycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon.ConclusionThe observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism.

Этногенетические аспекты ожирения и нарушений углеводного обмена как факторов риска артериальной гипертензии

Objective - to explore the association of candidate genes of arterial hypertension ACE, ADRA2B, ADRB1, MTHFR and eNOS with obesity and impaired glucose metabolism based on ethnicity. Materials and methods. Clinical and epidemiological study of compactly living population in the remote areas of the Mountain Shoria (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of these settlements were surveyed with the help of continuous sampling method; the sample consisted of adults (18 years and older). Results. In the group of respondents of the indigenous nationality averages Quetelet index, waist circumference and fasting blood glucose, depending on the polymorphism of candidate genes of arterial hypertension ACE, ADRA2B, ADRB1, MTHFR and eNOS were lower than in non-indigenous ethnic group surveyed. In a population of Shor was found a statistically significant relationship with the body mass index of ACE gene genotypes in a population of non-indigenous representatives - with genotypes of ADRA2B gene. In the group of indigenous ethnic group revealed the relationship from ACE gene polymorphism. Regardless of nationality, found associative connection of the indicator polymorphism of ADRA2B gene. The level of plasma glucose levels in a population of non-indigenous ethnic group was correlated with genotypes of ADRA2B gene. Conclusion. Metabolic abnormalities were detected less frequently in indigenous ethnic group compared with the non-indigenous. In Shor group ACE DD genotype and ADRA2B genes associated with obesity, the genotype 4a/4a eNOS gene - with abdominal obesity. In the group of non-indigenous ethnic group CC genotype of the MTHFR gene was associated with abdominal obesity, II genotype of ACE gene and DD ADRA2B gene - with impaired carbohydrate metabolism.

Association of angiotensin-converting enzyme I/D and α-actinin-3 R577X genotypes with metabolic syndrome risk factors in Korean children

This study analysed the risk factors associated with metabolic syndrome through the interaction between ACTN3 and ACE gene polymorphism in Korean children. The subjects of the study consisted of elementary school students (n=788, age 10.10±0.07 yr). The anthropometric parameters, blood lipid profiles, and metabolic markers were compared among groups of the ACE I/D or the ACTN3 R577X polymorphisms. The subjects with the DD genotype showed significantly higher systolic blood pressure than the subjects with the II and ID genotype of the ACE gene polymorphism. XX genotype had significantly lower waist-hip ratio than those with RR genotype of the ACTN3 gene polymorphism. Also, the subjects with XX genotype exhibited significantly higher blood HDL cholesterol level than those with RR or RX genotype. The interaction of ACTN3 and ACE gene polymorphism in subjects having both ACE DD and ACTN3 RR genotypes demonstrated a significantly higher metabolic syndrome score than any other groups. The children having both ACTN3 RR or RX genotype and ACE DD genotype showed high systolic blood pressure and low blood HDL cholesterol level, which may be considered a high-risk in metabolic syndrome.

O8. Cardiovascular risk factors, renin-angiotensin system gene polymorphisms, pregnancy course and outcomes in women with different forms of hypertension

Introduction The hypertensive disorders of pregnancy remain the leading causes of maternal and perinatal morbidity and mortality. Each form of hypertension during pregnancy has its outcome. The investigations of characteristics of genetic and cardiovascular risk factors in different forms of hypertension are necessary to carry out. Objectives The aim of our research was to study the frequency of cardiovascular risk factors, renin-angiotensin system gene polymorphisms, pregnancy course and outcomes in women with different forms of hypertension. Methods Prospective cohort study. The study included 300 patients (200 – with hypertension, 100 – without hypertension). Women with hypertension were divided into 4 groups: 106 patients with chronic hypertension (CH), 63 patients with gestational hypertension, 10 patients with preeclampsia (PE), 21 with PE superimposed on CH. Control group included 100 women without hypertension. Molecular genetic testing was used for detection of three polymorphic variants in angiotensin-converting enzyme (ACE I/D), angiotensinogen (AGT 174 T/M) and angiotensin II type 1 receptor (ATR1 1166 A/C) genes by polymerase chain reaction (“Lytech”, Russia). Statistical analysis was performed using the statistical software package version 11.5.0 MedCalc®. Gene-gene interactions were studied using entropy-based multifactor dimensionality reduction (MDR) method (software version 3.0.2). Results Pregnant women with CH and with PE superimposed on CH were more frequently of age over 35 years, overweight, obese and smoking and a high incidence of hypertension in the family history compared with pregnant women without hypertension. In pregnant women with CH a higher frequency of D allele and DD-genotype of ACE (I/D) and C allele of ATR1 (A1166C) were observed and compared with a control group. In pregnant women with PE a higher frequency of M allele and MM-genotype AGT (T174M) was noted. To assess independent associations of clinical and genetic factors with combined adverse outcome (fetal growth restriction or/and premature delivery or/and small gestational age) we have used MDR. The best interaction model included: age >35 years, hypertension in the family history, failure to achieve target blood pressure to 27–28 weeks and C allele of ATR1 (A1166C). The established model precisely predicted combined adverse outcome in 79.5% cases. Conclusion Analysis of cardiovascular risk factors, renin-angiotensin system gene polymorphisms may be helpful for evaluation adverse outcomes in pregnant women with different forms of hypertension.

DD Genotype of ACE I/D Polymorphism Might Confer Protection against Dental Caries in Polish Children

The aim of the study was to examine the frequencies of the genotypes and alleles of ACE insertion/deletion (I/D) polymorphism and their association with dental caries in a sample of Polish children. The study subjects were 120 children with dental caries experience (cases) and 41 caries-free individuals (controls). The genotyping was performed using polymerase chain reaction. The genotype distributions of ACE I/D polymorphism were not statistically different between carious and control children. However, we found a borderline overrepresentation of the II + ID genotypes versus the DD genotype in the carious compared to the control group (69.2% and 51.2%, respectively, p = 0.057). Logistic regression analysis adjusted for age and sex revealed that I allele carriage was a significant predictor of dental caries susceptibility (OR = 2.14, 95% CI = 1.02-4.49, p = 0.041). In conclusion, the DD genotype of ACE I/D polymorphism might be protective against dental caries in Polish children.

Gene-Pharmacologial Effects on Exercise-Induced Muscle Gene Expression in Healthy Men

Angiotensin 2 is a major vasoconstrictor and subject to complex regulation. It is produced by the angiotensinconverting enzyme (ACE), which is itself regulated by blood flow and represents a target for pharmacological (lisinopril) and genetical (ACE-I/D polymorphism) influences. 32 healthy Caucasian men of British descent, including six subjects that were treated with lisinopril, completed standardized one-legged cycling-type endurance exercise to assess ACE-I/D and lisinopril dependent levels alterations of ACE and hypoxia-modulated transcripts in knee extensor muscle. Lisinopril treatment revealed significantly decreased transcript expression at baseline (COX4I1-88%; COX4I2 -67%; HIF-1α -93%) and 3 hours into recovery (HIF-1α -78%; ACE -62%). Furthermore, during recovery from cycling-type endurance exercise, COX4I2 mRNA expression was increased by 281% in ACE-II genotypes (p <0.05) but not in subjects carrying the ACE D-allele. Additionally, ACE-DD genotypes showed a trend for superior expression of ACE mRNA (p =0.07), whereas for carriers of the ACE I-allele a decrease (ACE-ID-35%; ACE-II -67%) was observed. Changes in COX4I2 and ACE transcript expression were correlated to HIF-1α protein levels prior to exercise, which was highest in ACE-DD genotypes. The interpretative hypothesis is suggested that exercise-induced COX4I2 transcript expression is sensitized in dependence of the I-allele, which silences ACE expression. The findings implicate a pronounced influence of anti-hypertensive treatment on muscle gene expression, which is modified by the ACE-I/D genotype. The observed effects of lisinopril and the ACE I-allele suggests a possible role of shear stress and tissue oxygenation on the expression of oxygen-associated transcripts during recovery from the sympatholytic challenge of endurance exercise.

Association of Angiotensin Converting Enzyme Insertion-Deletion Polymorphism with Hypertension in Emiratis with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status.

The association of Angiotensin Converting Enzyme (ACE) insertion-deletion (I/D) polymorphism with Type 2 Diabetes Mellitus (T2DM) and hypertension has been extensively studied throughout various ethnic populations but largely with inconsistent findings. We investigated these associations in Emirati population and their interaction with obesity status. Saliva samples were collected from a total of 564 Emiratis (277 T2DM and 297 healthy). DNA was extracted and the samples were genotyped for ACE I/D polymorphism by a PCR based method followed by gel electrophoresis. Upon evaluation of the ACE I/D polymorphism amongst all T2DM, hypertensive patients, and respective controls regardless of obesity status, ACE DD genotype was not found to be associated with either T2DM [odds ratio (OR) = 1.34, p = 0.086] or hypertension [odd ratio (OR) = 1.02, p = 0.93]. When the genetic variants amongst the nonobese and obese population were analyzed separately, the risk genotype ACE DD conferred significantly increased risk of hypertension in nonobese population [odds ratio (OR) = 1.80, p = 0.02] but was found to be protective against the hypertension in the obese group ((OR) = 0.54, p = 0.01). However, there was no effect of obesity status on the association of ACE genotypes with T2DM. The risk of hypertension associated with ACE DD is modulated by obesity status and hence future genetic association studies should take obesity into account for the interpretation of data. We also confirmed that ACE I/D polymorphism is not associated with T2DM risk in Emirati population.

The impact of the genetic factor in the realization of the arterial hypertension and metabolic disorders at children with overweight or obesity

Essential arterial hypertension is a multifactor pathology and in its realization genetic and environmental factors play a very important role. It is estimated that 30-60% of the variation of the arterial hypertension among people is due to genetic factor. Its investigation is argued at children especially, because from age it can be changed under the influence of the environment. Objectives. Estimation of the polymorph variants frequency of the candidate genes from RAS (ACE, AGTR1) and NOS3 at children with arterial hypertension, obesity or overweight. Appreciation of the possible relations between carrying genotypes of the genes studied and the risk of arterial hypertension, overweight and metabolic disorders to appear. Interaction of the genetic factors with the modifiable ones in the appearance of these pathologies. Material and methods. The investigation included 120 children with obesity and overweight 62 (51.67%) children with hypertension and 58 (48.33%) with normal tension) at the age of 10-18. The polymorphism of the candidate genes was identified through the analysis of the length of the amplified fragments and restriction fragment length polymorphism. The products of restriction were placed in 2% agarose gel and dyed with ethidium bromide. The protocol of the studies was approved by the Commission in Medical Ethics and the signed consent for participation in studies was obtained. Results. Children-carriers of ACE DD and AGTR1 CC showed increased values of of BMI, CA and SBP. At the carriers of GG and AG genotypes of NOS3 AG were also revealed statistically significant higher values of SBP in comparison with the carriers of AA genotype. At the same time, children with ACE DD genotype were distinguished by the increased serum level of triglycerides (1.90 ± 0.122 mmol/l), insulin (27.27 ± 2.557 μU/ml) and reduced of HDL-C (1.24 ± 0.048 mmol/l). Simultaneously, there were found statistically significant differences between small gestational age and genotype DD of ACE and between big gestational age and genotype ID of ACE. DD carriers of the ACE and CC carriers of the AGTR1 also proved to be more often passive smokers, consumers of the products with higher concentration of salt and fat. Conclusion. Identification of the children with obesity/overweight carriers of genotypes ACE DD, AGTR CC and NOS GG could facilitate early detection of the children with the risk of appearance of arterial hypertension and metabolic disorders to add to taking early measures for prophylaxis and treatment.