DI Genotype Research Articles

Association ofGenotype, High-G Tolerance, andBody Composition inJet Aircraft Aviators.

Pilots of high-performance F15 and F16 jets must undergo periodic assessment of +8.5 Gz tolerance in a centrifuge, which is classified as a high-intensity exercise. Prior research has indicated that exercise performance may be correlated with alpha-actinin3 (ACTN3) and angiotensin-converting enzyme (ACE) genes, frequently termed the sports genes. This study aimed to investigate how ACTN3 and ACE genotypes correlate with high-g tolerance of Korean F15 and F16 pilots. A total of 81 Korean F15 and F16 pilots (ages 25-39 years) volunteered to participate in human centrifuge testing at +8.5 Gz. Exercise tolerance was calculated as the mean breathing interval during high-g tests, the target gene genotypes (ACTN3 and ACE) were identified, and body composition measurements were measured. The relationship among the ACTN3 and ACE genotypes, high-g tolerance, and body compositions were evaluated. The ACTN3 genotypes identified included 23 RR (28.4%), 41 RX (50.6%), and 17 XX (21.0%). The ACE genotypes identified included 13 DD (16.0%), 39 DI (48.2%), and 29 II (35.8%). Both genes satisfied an equilibrium check. In multivariate analysis by Roy's max, the interaction of the target genes (ACTN3 and ACE) was significant (P < .05). The ACTN3 gene showed significance (P < .05), while ACE tended toward significance with a correlation of P = .057 with high-g tolerance(s). Body composition parameters including height, body weight, muscle mass, body mass index, body fat (%), and basal metabolic rate showed no significant correlation with either genotype. In a preliminary study, the RR ACTN3 genotype showed a significant correlation with +8.5 Gz tolerance. Pilots with the DI genotype showed the highest high-g tolerance in this test; however, the test pass rate was higher in pilots with the DD genotype in the preliminary study. This result shows the possibility of test passing and tolerance superiority consisting of two different factors in the relationship between high-g tolerance and ACE genotype. This study showed that pilots with the RR + DI genotype had the highest high-g tolerance, which correlated with the presence of the R and D alleles of the ACTN3 and ACE genes, respectively. However, body composition parameters were not significantly correlated with genotype. These results could suggest a plural gene effect on high-g tolerance; further follow-up is required to determine the practical usage and applications of these results.

Polymorphisms of the PLAG1 and their relationships with body measurements and carcass traits of Ongole crossbred cattle

Pleomorphic adenoma gene 1 (PLAG1) is a member of the PLAG family which is associated with body size in various cattle breeds. This study investigated the association of PLAG1 polymorphisms to carcass traits and body measurement of Ongole crossbred (PO) cattle in Kebumen. Chest girth, body length, body height, withers height, waist height, live body weight, carcass weight, and carcass percentage were carefully measured and recorded. The DNA genome extractions were originated from blood samples that was collected via jugular vein. The extracted DNA template used to amplify two PLAG1 polymorphisms target, namely, g.48308C>T and g.32212 (19 bp indel). Identification of g.48308C>T from PLAG1 was done via PCR-RFLP technique using SacII, wherein the 19 bp indel was obtained from PCR products. One-way analysis of variance and independent sample t-test were carried out to quantify the obtained data. This present study revealed variation in both g.48308C>T SNP and 19 bp indel. Three genotypes, TT, TC, and CC, were found for g.48308C>T SNP. Whilst two genotypes DD and DI genotypes were found for 19 bp indel. Non-significant differences were found between PLAG1 polymorphisms and traits of interest observed in Kebumen PO cattle population.

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.

Insertion/deletions within the bovine FoxO1 gene and their association analysis with growth traits in three Chinese cattle breeds

FOXO1 (FKHR) gene, as a transcription factor, plays a vital role in animal growth and development, participating in many biological processes. The aim of this study was to ascertain Insertion/deletions (Indels) polymorphism within bovine FoxO1 gene in 679 Chinese adult cows and associate them with stature traits. Two Indels (named as Indel-3 and Indel-4, recorded as rs383545622 and rs525318770 in NCBI, respectively) were successfully genotyped by the Once PCR method, which was reliable, rapid and cost effective for simultaneous detection of two or more Indels. Indel-3 and Indel-4 were located at the second intron. All four different haplotypes (H1: D3D4, H2: I3D4, H3: D3I4, H4: I3I4) could be identified, and the D (del-) allele, DD (del-/del-) genotype and D3D4 haplotype retained the highest frequency. However, individuals with DI (D3I3, D4I4 or H1H4/H2H3 genotype) showed significantly better phenotypic traits than those with the other genotypes in Nanyang cattle, showing a hybrid vigor. The results implied that this DI genotype can be applied to early selective breeding to improve the productivity of Nanyang cattle. Our results suggested that these two Indels within the bovine FoxO1 gene might be used as genetic markers for marker-assisted selection (MAS) in cattle breeding and genetics.

Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality.

Background: The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptors and facilitates virus entry into the host cell. In the present study, we hypothesize that a functional insertion/deletion polymorphism-rs4646994 I/D and rs4240157 T > C in the ACE gene could be associated with SARS-CoV-2 infection and mortality. Methodology: This study included 117 consecutive COVID-19 patients and 150 age matched healthy controls (ACE2-rs4646994 I/D) and 100 age matched healthy controls with ACE2 rs4240157 T > C. We used Mutation specific PCR (MSP) for ACE2-rs4646994 I/D genotyping and amplification refractory mutation system (ARMS-PCR) for ACE2 rs4240157 T > C genotyping. Results: Results indicated that there were significant differences in the genotype distributions of ACE2-rs4646994 I/D polymorphisms (p < 0.030) and ACE2 rs4240157 T > C between COVID-19 patients and controls (p-values < 0.05). Higher frequency of DD genotype (48.71%) and D allele (0.67) was reported in COVID-19 patients than controls. Our results showed that the ACE2-DD genotype was strongly associated with increased COVID-19 severity (OR 2.37 (95%) CI = (1.19–4.70), RR = 1.39 (1.09–1.77), p < 0.013) and also a strong association was seen with ACE2-ID genotype with COVID-19 severity (OR 2.20 (95%) CI = (1.08–4.46), p < 0.020) in the codominant model. In allelic comparison, the D allele was strongly associated with COVID-19 severity (OR 1.58 (95% CI) (1.11–2.27), RR 1.21 (1.05–1.41) p < 0.010). A significant correlation of ACE2-I/D genotypes was reported with Age (p < 0.035), T2D (p < 0.0013), hypertension (p < 0.0031) and coronary artery disease (p < 0.0001). Our results indicated ACE2-DD genotype was strongly associated with increased COVID-19 mortality (OR 8.25 (95%) CI = (2.40 to 28.34), p < 0.008) and also ACE2-DD + DI genotype was strongly associated with increased COVID-19 mortality with OR 4.74 (95%) CI = (1.5214 to 14.7915), p < 0.007. A significant correlation was reported between COVID-19 patients and age matched controls (p < 0.0007). Higher frequency of heterozygosity TC (40%) followed by ACE2-CC genotype (24.78%) was reported among COVID-19 patients. Using multivariate analysis, ACE2–CT genotype was strong associated with SARS-CoV-2 severity with an OR 2.18 (95% CI) (1.92–3.99), p < 0.010 and also ACE2–CC genotype was linked with COVID-19 severity with an OR 2.66 (95% CI) (1.53–4.62), p < 0.005. A significant correlation of ACE2-T > C genotypes was reported with gender (p < 0.04), T2D (p < 0.035). ACE2-CC genotype was strongly associated with increased COVID-19 mortality OR 3.66 (95%) CI = (1.34 to 9.97), p < 0.011 and also ACE2-C allele was associated with COVID-19 mortality OR 2, 01 (1.1761–3.45), p < 0.010. Conclusions: It is concluded that ACE-DD genotype and D allele was strongly associated with increased COVID-19 patient severity. In addition, ACE I/D polymorphism were strongly associated with advanced age, diabetes and ischemic heart disease in COVID-19 patients whereas ACE-II genotype was a protective factor against the development of severe COVID-19. ACE2-DD genotype was strongly associated with increased COVID-19 mortality. Additionally, ACE2–CC and CT genotypes were strongly associated with COVID-19 severity. Therefore, our study might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.

Human Ace D/I Polymorphism Could Affect the Clinicobiological Course of COVID-19.

Introduction The coronavirus disease 2019 (COVID-19), that is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has spread rapidly worldwide since December 2019. The SARS-CoV-2 virus has a great affinity for the angiotensin-converting enzyme-2 (ACE-2) receptor, which is an essential element of the renin-angiotensin system (RAS). This study is aimed at assessing the impact of the angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphisms, on the susceptibility and clinical outcomes of the COVID-19 immunoinflammatory syndrome. Patients and Methods. A total of 112 patients diagnosed with COVID-19 between 1 and 15 May 2020 were enrolled in the study. ACE gene allele frequencies were compared to the previously reported Turkish population comprised of 300 people. Results The most common genotype in the patients and control group was DI with 53% and II with 42%, respectively. The difference in the presence of the D allele between the patient and control groups was statistically significant (67% vs. 42%, respectively, p < 0.0001). Severe pneumonia was observed more in patients with DI allele (31%) than DD (8%) and II (0%) (p = 0.021). The mortality rate, time to defervescence, and the hospitalization duration were not different between the genotype groups. Conclusion Genotype DI of ACE I/D polymorphism is associated with the infectious rate particularly severe pneumonia in this study conducted in the Turkish population. Therefore, ACE D/I polymorphism could affect the clinical course of COVID-19.

The effect of family history of hypertension and polymorphism of the ACE gene (rs1799752) on cardiac autonomic modulation in adolescents.

This study aims to analyze the behaviour of cardiac autonomic modulation in adolescents with a family history of hypertension along with polymorphism of the ACE gene (rs1799752). The study involved 141 adolescents, with a mean age of 14.89, divided into the following six groups: offspring of normotensive parents (ONP): DD, DI and II; and offspring of hypertensive parents (OHP): DD, DI and II. Blood pressure, body composition, family history of hypertension, sleep disorder, and sexual maturation were assessed for the groups' characterization. Afterwards, an electrocardiogram was performed, and oral mucosal cells were collected to analyze heart rate variability and genotypic research of angiotensin-converting enzyme. The main finding of this study was the decrease of vagal action in group OHP (genotype DD) relative to group ONP (genotype II): LF (%), 54.25±3.14 vs 39.33±3.80; HF (%), 45.74±3.14 vs 60.66±3.80; LF/HF, 1.48±0.23 vs 0.68±0.19. The results also showed changes in the variable diastolic blood pressure (DBP) in OHP (genotype DI) to ONP (genotype II) groups: 72.99±2.33 vs 63.27±1.72; and OHP (genotype DI) to ONP (genotype DD) groups. Adolescents with genotype DD and a family history of arterial hypertension present chances in cardiac autonomic modulation, the cardiac parasympathetic modulation is lower in these adolescents in comparison to participants of ONP + II group.

Association Between the ACE (I/D) Gene Polymorphism and Hepatocellular Carcinoma Risk in Egyptian HCV Patients

Background: Hepatocellular carcinoma is one of the most fatal malignancies worldwide and is related to many risk factors. Chronic HCV is associated with a 20–30-fold increased risk for HCC. Angiotensin-converting enzyme (ACE) is overexpressed in many cancers and plays a major role in angiogenesis and carcinogenesis. Aim: We aimed to elucidate the effect of the ACE I/D gene polymorphism in patients with HCV-related liver cirrhosis and HCC, and its relationship to clinical parameters. Patients and Methods: The study included 180 participants, cirrhotic (n=60), HCC (n=60) and control healthy subjects (n=60). Liver and renal function tests, alpha-fetoprotein, HCV antibodies and triphasic CT were assessed. ACE Gene polymorphism was assessed by Nested PCR. Results: We observed higher frequencies of DD (36.7%) and DI (51.7%) genotypes, along with the D allele (62.5%), in HCC patients compared to those of cirrhotic cases (10%, 40% and 30%, respectively) and control subjects (6.7%, 38.3%, and 25.8%, respectively). DD and DI genotypes increased the risk and predicted the occurrence of HCC by OR 25.932 and OR 6.354, respectively. The D allele conveys significant risk for HCC compared to control and cirrhotic groups with OR 4.785 and OR 3.889, respectively. Both DD genotype and D allele are significantly correlated with larger tumor size and metastasis. Conclusion: The ACE I/D polymorphism (DD genotype and D allele) is significantly associated with HCC risk in HCV patients and is correlated with increased tumor growth and advanced stage.

Angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphism in Egyptian children with congenital heart disease.

Congenital heart diseases (CHDs) are the leading cause of infant deaths worldwide. The relationship between angiotensin-converting enzyme (ACE) gene polymorphism and CHDs is not clear. The aim of this work is to assess the presence of an association between ACE I/D polymorphism and CHD in Egyptian population. Seventy CHD cases and 70 controls were incorporated in this study. DNA was isolated from their peripheral blood, and then ACE I/D gene polymorphism was tested by polymerase chain reaction (PCR). There was no significant difference among the frequencies of the DD, II, and DI genotypes in patients and controls (26 [37.1%], 37 [53.3%], and 4 [5.7%], 5 [6.7%]), 40 (57.2%), 28 (40%), respectively (p value = 1 and OR [95% CI] = 1.1). There was no significant difference between D allele (DD + DI) and II genotype distribution among patients and controls (p value = 1 and OR [95% CI] = 1.2 [0.3-2.9]). Moreover, there was no difference between I allele (II + DI) and DD frequency (p value = 0.2 and OR [95% CI] = 0.6 [0.3-1.2]). ACE I/D gene polymorphism might not be a risk factor of CHD in Egyptian children. Additional widespread studies are needed to affirm these data.

Effects of angiotensin converting enzyme gene polymorphism on hypertension in Africa: A meta-analysis and systematic review.

BackgroundHypertension is dramatically increasing in Africa with evidence of increased severity and resistance to treatment. Although angiotensin converting enzyme gene polymorphism is associated with higher prevalence of hypertension, the evidence is inconclusive on its influence on the emerging pattern in Africa. This meta-analysis is conducted to pool the available evidence to inform future research and interventions.MethodsArticles published through May 2018 were systematically searched in PubMed, Scopus and EMBASE databases. Studies were assessed for inclusion by two independent researchers. Six models were used to assess the effect of angiotensin converting enzyme deletion-insertion gene polymorphism. Heterogeneity and publication bias were tested and sensitivity analysis was carried out. Odds ratio and 95% confidence intervals were measured for pooled effect. Both random effect and fixed effect models were used, whilst the frequency of DD, II and DI genotypes were computed and compared.ResultPatients with D allele were 1.49 times more likely to develop essential hypertension compared with patients who carry the I allele (OR:1.49; CI:1.07, 2.07). Similarly, patients who had homozygous co-dominance genotype DD (i.e., DD vs II) were at a 2.17 times higher risk of essential hypertension compared to the co-dominant genotype II (OR:2.17, CI:1.79, 3.18), dominant model (I.e., DD+ID vs II) (OR:1.48; CI:1.03, 2.12), and recessive model (OR:1.64; CI:1.03, 2.61). On subgroup analysis, participants from Sub-Saharan Africa were more genetically susceptible to hypertension compared to their North Africa counterparts. There was no publication bias found, but there was high to moderate heterogeneity.ConclusionACE I/D polymorphism is associated with essential hypertension in Africa in the allele contrast model, as well as the dominant, recessive and homozygous codominance model. On subgroup analysis, ACE I/D was associated with essential hypertension in patients from Sub-Saharan Africa but not in North Africa. A future large scale study, which includes different ethnic groups, is recommended.

Polymorphisms in the Uncoupling Protein 2 Gene Are Associated with Diabetic Retinopathy in Han Chinese Patients with Type 2 Diabetes.

The uncoupling protein 2 (UCP2) gene plays an important role in the complications of type 2 diabetes (T2D). However, the association between variants in the UCP2 gene and diabetic retinopathy (DR) in Han Chinese T2D patients remains unclear. Two single-nucleotide polymorphisms (SNPs) [rs659366 (-866G/A) and a 45-bp insertion/deletion (I/D) in the 3'-UTR] in the UCP2 gene were genotyped in a study cohort of 209 T2D patients with DR and 199 T2D patients without DR by direct DNA sequencing. Logistic regression analysis showed that the AA and GA genotypes of rs659366 were significantly associated with an increased risk for nonproliferative DR (NPDR) in the codominant model (corrected p-value <0.01) and the dominant model (corrected p-value = 0.006). Patients harboring the II and DI genotypes had a higher risk for PDR in the codominant model (corrected p-value = 0.011) and the dominant model (corrected p-value = 0.006), and the DI genotype showed a higher risk for NPDR in the dominant model (corrected p-value = 0.007) or codominant model (corrected p-value = 0.006). Further, haplotype analyses verified that the A-I haplotype is a risk haplotype for NPDR and PDR. This study suggests that the UCP2 gene may be involved in the pathogenesis of NPDR and PDR in Han Chinese patients with T2D.

Interaction of renin-angiotensin system gene polymorphisms with hypertension in Chinese patients with type 1 diabetes and retinopathy.

BackgroundThe objective of this research was to investigate the interaction of RAS gene polymorphisms in Chinese patients with type 1 diabetes mellitus (T1DM) and diabetic retinopathy (DR).MethodsGenomic DNA was extracted from peripheral blood leukocytes and genotyping for the angiotensin converting enzyme (ACE) gene I/D and angiotensinogen (AGT) gene M/T polymorphisms was performed using the polymerase chain reaction method. 311 T1DM patients were recruited for the assessment of ACE and AGT polymorphisms relating to DR.ResultsCompared with the diabetic non-retinopathy (DNR) patients, DR patients had lower proportion of diabetic nephropathy (p<0.001) and M allele (p=0.013). Intriguingly, the frequency D allele (p=0.035) was lower in DR patients with hypertension, as well as DD (p=0.003) and DI genotype (p=0.012) in DR patients with normal blood pressure after multiple tests with Bonferroni correction, but D allele (p=0.025) displayed higher in normotensive patients with T1DM. Logistic regression analyses indicated that no significant relationship existed about the genotype and allele polymorphisms with the progress of DR after adjusting for confounding factors.ConclusionsInteraction of hypertension and the RAS gene polymorphisms might have a role in the DR development in Chinese T1DM patients.

Polycystic Ovary Syndrome is Affected and Protected by DD and DI Genotypes of Angiotensin Converting Enzyme, Respectively: An Update of a Meta-Analysis

Objectives: Angiotensin converting enzyme (ACE) is an important enzyme involved in the physiopathology of renal, cardiovascular and ovarian systems. One of these ACE related diseases is polycystic ovary syndrome (PCOS). Materials and Methods: We intend to update the only meta-analysis written by Jia et al in 2013 on the association of ACE gene polymorphism and risk of PCOS. The reason of our attempt to update this meta-analysis was that they found no significant relation in their meta-analysis. For this aim, we searched in databases for relevant documents. Results: We found 8 relevant papers, 6 of which had been covered by Jia et al meta-analysis. In order to perform this meta-analysis, we used comprehensive meta-analysis software. The analysis was done through P value and sample size of each study based on fixed-effect model. Analyses were performed in 5 different groups of alleles and genotypes. Among these 5 analyses, 4 of them were statistically significant. Hereby, we concluded that DD genotype of ACE is a risk factor for PCOS (P value = 0.013; odds ratio [OR] = 1.195), while DI is the protecting genotype (P = 0.009; OR = 0.819). Conclusion: Hence, it is suggested to use a very low dose of captopril as an ACE inhibitor in the PCOS patients having DD genotype in future as a clinical trial, just as a scientific model. Further investigation on ovary ACE system is needed. Keywords Author Keywords:Angiotensin converting enzyme inhibitors; Meta-analysis; Polycystic ovary syndrome KeyWords Plus:INSULIN-RESISTANCE; GENE POLYMORPHISM; PCOS; WOMEN; STIMULATION; ASSOCIATION; EXPRESSION; ESTRADIOL; SYSTEM; RISK

Correlations between ACE single nucleotide polymorphisms and prognosis of patients with septic shock.

The aim of the present study is to investigate association between septic shock (SS) and angiotensin I-converting enzyme (ACE) single nucleotide polymorphisms (SNPs). From October 2009 to December 2016, 238 SS patients and 242 healthy individuals were selected for our study. ACE activity was detected, ACE rs4291 and rs4646994 polymorphisms were detected using PCR-restriction fragment length polymorphism (PCR-RFLP). The Kaplan–Meier survival curve was employed to evaluate the association between ACE SNPs and patients’ survival and univariate and multivariate analyses to estimate risk factors for SS. ACE activity in the case group was increased in comparison with the control group. Allele and genotype frequencies of rs4291 and rs4646994 were different between the case and control groups. The TT genotype frequency of the rs4291 polymorphisms and the DD genotype of the rs4646994 polymorphisms of the case group were higher than those in the control group. The AT and TT genotypes indicated a significant elevation of ACE activity than the AA genotype, while a significant decline was found in the DI and II genotypes in comparison with the DI genotype. Patients with TT or DD genotypes had increased fatality rate within 7 and 30 days when compared with those with non-TT or non-DD genotypes. Lower sepsis-related organ failure assessment (SOFA) scores, rs4291, serum ACE and rs4646994 were all considered as risky factors for SS patients. The study demonstrates that TT genotype of rs4291 or DD genotype of rs4646994 may be indicative of a higher risk of SS and a poorer prognosis in SS patients.

Association Between ACE Gene Polymorphism and QT Dispersion in Patients with Acute Myocardial Infarction.

Background:Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI).Objective and Methods:The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated.Results:The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude of the QT dispersion prolongation was higher in patients carrying the ACE D allele than patients who were not carrying it, at baseline and at the end of six-month follow up (52.5 ±2.6 msn vs. 47.5±2.1 msn at baseline, 57±3.2 msn vs. 53±2.6 msn in months, P: 0.428 and P: 0.613, respectively).Conclusion:Carriers of the D allele of ACE gene I/D polymorphism may be associated with QT dispersion prolongation in patients with MI.An interaction of QT dispersion and ACE gene polymorphism may be associated with an elevation of serum type I-C terminal pro-collagen concentration, possibly leading to myocardial fibrosis, and increased action potential duration.

Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure.

BackgroundAssociation between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association.ObjectivesTo assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings.MethodsGenetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients.ResultsThe allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD.ConclusionsMore DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD.

Correlation of ACE gene deletion/insertion polymorphism and risk of pregnancy-induced hypertension: a meta-analysis based on 10,236 subjects.

To clarify the association of angiotensin-converting enzyme (ACE) gene deletion/insertion polymorphism with risk of pregnancy-induced hypertension. We systematically searched China National Knowledge Infrastructure, Wanfang database, Chongqing WeiPu database and PubMed up to March 2014 to collect related case-control studies. RevMan 5.0 software was used for meta-analysis after evaluating the quality of enrolled studies and extracting the data. A total of 45 case-control studies was selected, including 10,236 subjects. The meta-analysis was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) after genotype consolidation. In total, D allele vs I allele: OR 1.57, 95% CI 1.33-1.86; genotype DD vs genotype II + DI: OR 1.86, 95% CI 1.48-2.32; genotype II vs genotype DI + DD: OR 0.65, 95% CI 0.53-0.80. In the Asian population, D allele vs I allele: OR 1.80, 95% CI 1.36-2.38; genotype DD vs genotype II + DI: OR 2.25, 95% CI 1.53-3.30; genotype II vs genotype DI + DD: OR 0.56, 95% CI 0.41-0.76. In the Caucasian population, D allele vs. I allele: OR 1.24, 95% CI 1.08-1.44; genotype DD vs. genotype II + DI: OR 1.25, 95% CI 1.10-1.41; genotype II vs. genotype DI + DD: OR 0.96, 95% CI 0.83-1.11. The ACE gene insertion/deletion polymorphism is associated with the risk of pregnancy-induced hypertension.

Study of correlation between polymorphism of ST6GALNAC2 and susceptibility to IgA nephropathy.

The aim of the present study was to explore the correlation between single nucleotide polymorphisms (SNPs) rs3840858 and rs2304921 in a specific α-2,6 sialyltransferase gene, ST6GALNAC2, and the susceptibility to immunoglobulin (IgA) nephropathy (IgAN). The distributions of genotypes of SNPs rs3840858 and rs2304921 in ST6GALNAC2 were detected by direct sequencing. The distributions of the genotype and allele frequencies of rs3840858 in patients with IgAN were significantly different from those in the control group (genotypes, P=0.001; alleles, P=0.001). The DI genotype ratio (17.8%) in the IgAN group was higher than that in the control group (5.6%) and the I allele frequency (8.9%) in the IgAN group was higher than that in the control group (2.8%). Univariate logistic regression analysis indicated that rs3840858 polymorphism is a risk factor of IgAN (P=0.001). The risk of developing IgAN in individuals who carried the DI genotype was 3-fold higher than that in individuals who carried the DD genotype [odds ratio (OR)=3.676, 95% confidence interval (CI)=1.284-10.519], and the risk of developing IgAN in individuals who carried the I allele was higher than that in individuals who carried the D allele (OR=3.415, 95% CI=1.223-9.531). The distributions of the genotype (AA, AG and GG) and allele (A and G) frequencies of rs2304921 did not have a statistically significant difference between patients with IgAN and those without (P>0.05). The SNP rs3840858 in the ST6GALNAC2 gene may be associated with the risk of developing IgAN in the population studied; however, polymorphism of rs2304921 appears to be irrelevant to the risk of developing IgAN in this population.

Association between C1GALT1 variants and genetic susceptibility to IgA nephropathy in Uygur.

Immunoglobulin A (IgA) nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition leading to mesangial proliferation and chronic glomerular inflammation. Analyses of serum IgA1 from IgAN patients revealed abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may result from altered activity in the core of 1 b1,3-galactosyltransferase (C1GalT1). To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case-control study on cohorts from the Uyghur population in China. A total of 180 IgAN patients and 180 healthy controls were recruited for the study. We sequenced 5 SNPs, including SNP1 (rs9639031), SNP2 (-527A/G), SNP3 (rs1008898), SNP4 (rs5882115), and SNP5 (rs1047763) in the C1GalT1 gene in all eligible participants. The frequencies of the I allele and DI genotype of rs5882115 in IgAN patients were significantly higher than those in controls (P < 0.05). The frequency of haplotype GAGDA was significantly higher in patients than in controls (0.0719 vs 0.00, P = 0.024). Polymorphisms in the C1GALT1 gene were associated with genetic susceptibility to Uyghur IgAN.

Effects of l-arginine supplementation on blood pressure reduction pre-, peri-, and post-cardiovascular stimulus in hypertensive subjects with different angiotensin-converting-enzyme genotypes

PurposeThe present study investigated whether L-arginine supplementation reduces blood pressure (BP) in hypertensive subjects with different ACE genotypes.MethodsEight male hypertensive patients received L-arginine (2 or 4 g/day) or a placebo for a period of 4 days prior an exercise test. Statistical analysis consisted of one-way analysis of variance.ResultsL-arginine supplementation induced a statistically significant (&lt;i&gt;p&lt;/i&gt; &gt; 0.05) reduction in systolic BP measured during rest (reductions of 7.8% and 12.3% with 2 and 4 g/day, respectively), exercise (reductions of 11.8% and 10.4% with 2 and 4 g/day, respectively), and recovery (reductions of 11.7% and 10.7% with 2 and 4 g/day, respectively). The observed magnitude of BP reduction suggests an association with ACE polymorphism; a larger effect was seen with the II and DI genotypes compared with the DD genotype (II: 121 mmHg and DI: 133 mmHg vs. DD: 144 mmHg).ConclusionsThe results showed that L-arginine supplementation at low doses was efficient in reducing BP and that vasodilator actions that occurred through the secretion of nitric oxide might be ACE genotype dependent.