DD Polymorphism Research Articles

Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension.

The renin-angiotensin-aldosterone system was shown to be activated in severe COVID-19 infection. We aimed to investigate the relationship between angiotensin converting enzyme (ACE) levels, ACE gene polymorphism, type 2 diabetes (T2DM), and hypertension (HT) and the prognosis of COVID-19 infection. This cross-sectional study analyzed the clinical features of adult patients with SARS-CoV-2 infection. ACE gene analysis and ACE level measurements were performed. The patients were grouped according to ACE gene polymorphism (DD, ID or II), disease severity (mild, moderate, or severe), and the use of dipeptidyl peptidase-4 enzyme inhibitor (DPP4i), ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARB). Intensive care unit (ICU) admissions and mortality were also recorded. A total of 266 patients were enrolled. Gene analysis detected DD polymorphism in the ACE 1 gene in 32.7% (n = 87), ID in 51.5% (n = 137), and II in 15.8% (n = 42) of the patients. ACE gene polymorphisms were not associated with disease severity, ICU admission, or mortality. ACE levels were higher in patients who died (p = 0.004) or were admitted to the ICU (p<0.001) and in those with severe disease compared to cases with mild (p = 0.023) or moderate (p<0.001) disease. HT, T2DM, and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission. ACE levels were similar in patients with or without HT (p = 0.374) and with HT using or not using ACEi/ARB (p = 0.999). They were also similar in patients with and without T2DM (p = 0.062) and in those with and without DPP4i treatment (p = 0.427). ACE level was a weak predictor of mortality but an important predictor of ICU admission. It predicted ICU admission in total (cutoff value >37.092 ng/mL, AUC: 0.775, p<0.001). Our findings suggest that higher ACE levels, but not ACE gene polymorphism, ACEi/ARB or DPP4i use, were associated with the prognosis of COVID-19 infection. The presence of HT and T2DM and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission.

Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.

Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop severe COVID-19. We conducted a systematic review of current evidence to investigate the association of genetic variants of these genes with the susceptibility to virus infection and patient prognosis. We systematically searched Medline, Embase and The Cochrane Library for articles published until May 2022, and included observational studies covering genetic association of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes with COVID-19 susceptibility or prognosis. We evaluated the methodological quality of included studies, and pooled data as convenient in meta-analysis (MA). Odds ratio (OR) values and 95% confidence intervals were calculated. We included 35 studies (20 on ACE, 5 each on IFITM3, TMPRSS2, TNFα), enrolling 21,452 participants, of them 9401 were COVID-19 confirmed cases. ACE1 rs4646994 and rs1799752, ACE2 rs2285666, TMPRSS2 rs12329760, IFITM3 rs12252 and TNFα rs1800629 were identifies as common polymorphisms. Our MA showed an association between genetic polymorphisms and susceptibility to SARS-CoV-2 infection for IFITM3 rs12252 CC (OR 5.67) and CT (OR 1.64) genotypes. Furthermore, MA uncovered that both ACE DD (OR 1.27) and IFITM3 CC (OR 2.26) genotypes carriers had a significantly increased risk of developing severe COVID-19. These results provide a critical evaluation of genetic polymorphisms as predictors in SARS-CoV-2 infection. ACE1 DD and IFITM3 CC polymorphisms would lead to a genetic predisposition for severe lung injury in patients with COVID-19.

Diagnostic efficacy of cystatin-c in association with different ACE genes predicting renal insufficiency in T2DM

Diabetic nephropathy (DN) seems to be the major cause of chronic kidney disease that may finally lead to End Stage Renal Disease. So, renal function assessment in type 2 diabetes mellitus (T2DM) individuals is very important. Clearly, DN pathogenesis is multifactorial and different proteins, genes and environmental factors can contribute to the onset of the disease. We assessed sensitive and specific biomarkers (in blood and urine) which can predict kidney disease susceptibility among T2DM patients. Serum cystatin-c (cyst-c) in blood and urinary hemeoxygenase (HO-1) in addition to ACE I/D polymorphism and ACE G2350A genotypes. Hundred and eight T2DM patients and 85 controls were enrolled. Serum cystatin-c and urinary (HO-1) were tested by ELISA. Genetic determination of both ACE I/D polymorphism and ACE G2350A genotypes was performed by PCR for all participants. Significant rise in serum cystatin-c and urinary HO-1 levels were shown in diabetic groups compared with control group. Moreover, GG genotype of ACE G2350A gene in diabetic group was associated with rise in serum cystatin-c and urinary HO-1 compared with control group. Mutant AA genotype demonstrated increase in urinary HO-1. DD polymorphism was associated with rise in serum creatinine and cyst-c in diabetic group. Positive correlation was seen between duration of diabetes and serum cyst-c and between serum glucose and urinary (HO-1) in diabetic group. The results from this study indicated an association of serum cystatin-c with GG genotype of ACE G2350A in conjugation with DD polymorphism of ACE I/D which could be an early predictor of tubular injury in T2DM diabetic patients.

Angiotensin Converting Enzyme 1 Polymorphisms and Lipid Profile in Mexican Patients With COVID-19.

Renin-angiotensin system (RAS) is present in a diverse type of cells and plays an important role in lung physiology and pathophysiology. Angiotensin converting enzymes (ACE) are part of the RAS system. There are still controversies about the association of I/D polymorphisms of ACE1 with COVID-19 severity. The goal of the study was to determine whether there is an association of the I/D polymorphism with severity of COVID-19 in Mexican patients. The study included voluntary participants: 53 healthy individuals negative to RT-PCR COVID-19 (control), and 165 patients positive to COVID-19. Severity was defined by the need of hospitalization, invasive ventilation, shock, or multiple organ failure. The patient group consisted of 28 asymptomatic, 82 with mild, and 55 with severe COVID-19. I/D polymorphism was determined by PCR. Rutinary laboratory tests were performed in all the participants. DD polymorphism was significantly associated with severe COVID-19, independently of comorbidities, or any other variable. Receiver operator characteristic curves demonstrated association of low total cholesterol, low high-density lipoproteins, and high c-reactive protein with severity of COVID-19. The DD polymorphism was associated with the course of the infection and severity of COVID-19 in a sample of Mexican patients.

ACE Insertion/Deletion gene polymorphism aassociations in STEMI Patients

Abstract Objective ACE Insertion/deletion (I/D) polymorphism has been reported to be associated with various cardiovascular conditions, however its impact in patients with AHF remains controversial. This study aimed to analyze ACE I/D distribution, rate of acute heart failure (AHF) and survival in ST segment elevation myocardial infarction (STEMI) patients. Methods Genomic DNA from 245 STEMI patients and 87 healthy control subjects were analyzed by single polymerase chain reaction method. Based on the ACE I/D genotype STEMI patients were divided with AHF/no AHF, and then - for preserved/reduced ≤40% left ventricle (LV) ejection fraction (EF) to investigate the frequency of the mutant allele D. Results ACE gene polymorphism analyses revealed that D allele had been found more often in STEMI patients than in controls (84.1 vs. 72.4%). The frequency of II, ID, and DD genotypes in STEMI patients was 27.6%, 52.9% and 19.5% compared to 15.9%, 54.3% and 29.8%, respectively in controls with a significant difference in mutant homozygous genotype. Distribution of I/D ACE gene variants among AHF cases vs no AHF, showed similar frequency of II allele (15.8 vs 13.5%), ID allele (54.9 vs 52.8%) and DD allele (29.3 vs 33.7% respectively). In patients with preserved EF there was not statistical significance among different alleles with and without AHF. However, ACE DD polymorphism has been found in AHF patients with reduced EF significantly more often (50.0 vs 30.5%; p&amp;lt;0.05) in compare to AHF patients with preserved EF. Finally, cardiovascular death among all STEMI patients during 3-year follow up was more frequent in patients with DD allele (17.7% vs 5.7% with II and vs 9.9% with ID allele). Conclusion Presented results confirmed ACE DD polymorphism to be associated with higher rate of cardiovascular death and presence of AHF with reduced LV EF in STEMI patients. Future studies are needed to evaluate importance of ACE DD polymorphism in order to find optimal treatment strategies and to prevent negative outcomes in those patients. Funding Acknowledgement Type of funding sources: None.

Polymorphism in Apolipoprotein C3 (APOC3) and Fatty Acid-Binding Proteins (FABP2) Genes in Nondiabetic Dyslipidemic Patients: A Tertiary Care Hospital-Based Pilot Study

Context Dyslipidemia is a multifactorial disease in which lipoproteins play an important role as one of the early markers for coronary heart disease (CHD). Mixed dyslipidemia is common in people with diabetes mellitus, but nondiabetic dyslipidemics (NDD) remain unidentified for the risk of developing dyslipidemia and eventually CHD. Objectives This pilot study attempts to analyze the genetic basis of lipid metabolism alterations, emphasizing the association between fatty acid-binding protein-2 (FABP2-Ala54Thr) and apolipoprotein-C3 (APOC3-rs5128) genetic polymorphism, as a risk for developing dyslipidemia and CHD in NDD. Methods and Design Total 90 subjects—30 DD, 30 NDD, and 30 apparently healthy subjects representing Central India—were included. Biochemical analysis and DNA genotyping were done by polymerase chain reaction restriction fragment length polymorphism. Statistical Analysis The biochemical parameters were reported as means ± standard deviation. One-way analysis of variance test was used to compare biochemical parameters of three groups. Chi-squared test was done to compare genotype distributions. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). All statistical analysis was done using SPSS-PC software and Graph Pad. Results In NDD, maximum polymorphism was observed followed by DD and least polymorphism was observed in controls. There was a significant association of APOC3 G allele with occurrence of hypertriglyceridemia ( p < 0.05); however, no such association was found for FABP2 A allele ( p > 0.05). Logistic regression analysis revealed APOC3 polymorphism to be significantly associated with dyslipidemia (OR = 2.6667, 95% CI = 1.0510–6.7663, p = 0.0341); no such association was found for FABP2 polymorphism (OR = 0.4643, 95% CI = 0.1641–1.3136, p = 0.1347). The triglyceride and cholesterol values in individuals with homozygous genotype indicate that genetic study is comparable to the biochemical findings in carriers of polymorphic allele than noncarriers, especially in NDD patients. Conclusions Pilot study indicates that the presence of APOC3 gene polymorphism is associated with pro-atherogenic dyslipidemia in nondiabetic patients and may raise risk of CHD. This information could be used for preventive strategies in NDD group that may otherwise go unnoticed.

Influence of ACE Gene I/D Polymorphism on Cardiometabolic Risk, Maximal Fat Oxidation, Cardiorespiratory Fitness, Diet and Physical Activity in Young Adults.

There is controversy about the relationship between ACE I/D polymorphism and health. Seventy-four healthy adults (n = 28 women; 22.5 ± 4.2 years) participated in this cross-sectional study aimed at determining the influence of ACE I/D polymorphism, ascertained by polymerase chain reaction, on cardiometabolic risk (i.e., waist circumference, body fat, blood pressure (BP), glucose, triglycerides, and inflammatory markers), maximal fat oxidation (MFO), cardiorespiratory fitness (maximal oxygen uptake), physical activity and diet. Our results showed differences by ACE I/D polymorphism in systolic BP (DD: 116.4 ± 11.8 mmHg; ID: 116.7 ± 6.3 mmHg; II: 109.4 ± 12.3 mmHg, p = 0.035) and body fat (DD: 27.3 ± 10.8%; ID: 22.6 ± 9.7%; II: 19.3 ± 7.1%, p = 0.030). Interestingly, a genotype*sex interaction in relativized MFO by lean mass (p = 0.048) was found. The DD polymorphism had higher MFO values than ID/II polymorphisms in men (8.4 ± 3.0 vs. 6.5 ± 2.9 mg/kg/min), while the ID/II polymorphisms showed higher R-MFO values than DD polymorphism in women (6.6 ± 2.3 vs. 7.6 ± 2.6 mg/kg/min). In conclusion, ACE I/D polymorphism is apparently associated with adiposity and BP, where a protective effect can be attributed to the II genotype, but not with cardiorespiratory fitness, diet and physical activity. Moreover, our study highlighted that there is a sexual dimorphism in the influence of ACE I/D gene polymorphism on MFO.

IMPACT OF ANGIOTENSIN-1 CONVERTING ENZYME GENE INSERTION/DELETION (I/D) POLYMORPHISM ON DIABETES MELLITUS SUSCEPTIBILITY AMONG AZERBAIJAN POPULATION

The association between the angiotensin‑converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the risk of diabetes mellitus developing in the Azerbaijan population is not studied yet. Therefore, the aim of the present study was to investigate the association of ACE I/D gene polymorphism and the risk of developing diabetes in Azerbaijan population. A total of 200 individual consisting of 100 control subjects and 100 patients with diabetes mellitus (28 patients I type DM (11 male and 17 female); 72 patients II type DM (21 male and 51 female)) were recruited. DNA was extracted from the blood samples. Genotyping of ACE I/D gene polymorphism done by PCR and mistyping of the II and DD genotypes was conducted with an insertion/deletion‑specific primer. The genotyping frequency for the II, ID and DD polymorphism of the ACE gene ID=63, DD=36, II=1 in case subjects. The genotyping frequency for the II, ID and DD polymorphism of the ACE gene in control group: ID=49, DD=26, II=25. The frequency for the D allele is 67.5 and the frequency of I allele is 32.5 in case group. The frequency for the D allele is 50.5 and the frequency of I allele is 49.5 in control group. The dominant and recessive models revealed alleles on separate groups and at the population level: DD:DR=13.6; ID:IR=15; ID:DD=0.35; DD:ID= 2.97; DR: IR=3.26; IR:DR=0.3. Based on the results, D allele showed significant association with risk of disease. This finding revealed the association of I/D polymorphism with risk of diabetes. However, further studies with larger sample size are necessary to confirm the association of the I/D polymorphism of the ACE gene and diabetes mellitus in Azerbaijan population.

ACE DD polymorphism in severe COVID-19

ACE DD polymorphism in severe COVID-19

Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

RationaleHypertension, obesity and diabetes are major risk factors associated with morbidities underlying COVID-19 infections. Regression analysis correlated presence of ACE insertion/deletion (I/D) polymorphism to COVID-19 incidence and mortality. Furthermore, COVID-19 prevalence correlated to allele frequency of angiotensin-converting enzyme (ACE) deletion (D) polymorphism within the European population.ObjectiveHomozygous ACE deletion polymorphism is associated with increase in ACE and angiotensin II (Ang-II), sustained levels can result in inflammation, fibrosis and organ damage. The ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for COVID-19 infection and outcomes. The study objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities providing rationale for therapeutic utility of ACE-I/ARBs to improve outcomes.Method and ResultsThe Allele Frequency Database (ALFRED) was queried for frequency of rs4646994 representing ACE I/D polymorphism. In a total of 349 worldwide population samples, frequency of ACE D allele was higher in European, Asian, and Africans cohorts. In the USA, the frequency of ACE D allele was higher in non-Hispanic Black compared with non-Hispanic White and Mexican Americans.ConclusionCOVID-19 binding mediated reduction/inactivation of ACE-II can increase ACE/Ang-II signalling pathway and related pathologies. The presence of ACE DD polymorphism with COVID-19 infection likely augments ACE/Ang-II activities, increasing severity of COVID-19 morbidities and impacts outcomes. Thus, ethnic prevalence of ACE DD polymorphism can explain in part the severity of COVID-19 morbidity providing rationale for the use of ACE-I/ARBs to improve outcomes.

Evaluation of the effect of serum cystatin-C and ACE I/D and ACE G2350A polymorphisms on kidney function among hypertensive sewage workers.

Cadmium (Cd) as nephrotoxicant metal exerts its potent effect mainly on renal tubules disturbing its functions. A cross-sectional study was conducted on 55 sewage workers occupationally exposed to Cd and 50 control subjects. The study aimed to assess the effect of low-level Cd exposure on blood pressure and renal function in terms of serum cystatin-C levels. The associations between genetic polymorphisms of ACEI/D and ACE G2350A and hypertension and tubular injury among workers were studied. We analyzed blood and urine Cd concentration (U-Cd), serum cystatin-C, ACE I/D polymorphisms, and ACE G2350A, and blood pressure was measured. Results recorded a significant rise in serum and U-Cd and cystatin-C levels in sewage workers compared with controls. Significant distribution in genotype frequency of ACE I/D and ACE G2350A gene was detected. An association in DD genotype of ACE I/D with a rise in serum and U-Cd was observed in workers. In wild type genotype GG of ACE G2350A gene, a significant rise in serum cystatin-C levels and diastolic pressure was found while in heterozygote genotype GA significant rise in U-Cd levels was detected. Also, the association of AA genotype of ACE G2350A gene with a significant rise in serum and U-Cd and cystatin-C levels was shown among workers compared with control groups. Our findings indicated an association of ACE DD polymorphism in conjugation with GG genotype of ACE2 with hypertension and tubular injury in sewage workers.

Testing for the Association Between ACE DD (RS1799752) Polymorphism and the Metabolic Syndrome in Patients with Hypertension

High blood pressure (HBP) is a complex multifactorial condition which has a polygenic predisposition. The angiotensin-converting enzyme (ACE) is one of the candidate genes for HBP, and the ACE ID polymorphism with DD genotype presents a high risk for myocardial infarction, obesity (OB), stroke, type 1 diabetes mellitus (DM1), type 2 diabetes mellitus (DM2), diabetic nephropathy. The purpose of the study is to identify the high risk of developing MS in ACE DD gene (RS1799752) on the basis of clinical data, biochemical laboratory investigations, genotyping and sequencing of ACE gene in patients with HBP, by using the mathematical algorithm ANOVA One Way as a linear model, with the help of the MDR, Graph Pad Prism and MATLAB software. This study includes 68 subjects, selected from Giurgiu County Emergency Hospital based on clinical data, biochemical investigations, RFLP-PCR genotyping and Advanced NGx sequencing of the ACE gene with the DD genotype to identify the increased risk of developing metabolic syndrome (MS) in patients with hypertension. The results was taken by using as a linear model the mathematical algorithm ANOVA One Way using the programs MDR, Graph Pad Prism and MATLAB. In conclusion the ACE DD polymorphism is significantly associated with MS in patients with hypertension.

Evaluation of common polymorphisms of eNOS gene and ACE gene in autosomal dominant polycystic kidney disease patients and their association with hypertension and renal failure

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most hereditary renal disease that leads to end-stage renal disease (ESRD). Objectives: Since there is no available parameter to assess the clinical course of ADPKD and its outcome, yet, the aim of our study was evaluation of the association of common polymorphisms of eNOS and ACE genes with clinical manifestations (kidney failure and hypertension) in ADPKD. Patients and Methods: Seventy-five ADPKD patients and 100 control subjects participated in our study. Around 7.5 cc of whole blood was taken from each participant and sent to the genetic laboratory. DNA was obtained from them by the phenol chloroform extraction and ethanol precipitation techniques. Then genotyping for I/D polymorphism of ACE gene and Glu298 ASP and T786C polymorphisms of eNOS gene was performed by PCR electrophoresis and molecular evaluation by special primers for two genes. Results: The frequency of DD polymorphism of ACE gene and TC polymorphism of T786C of eNOS were considerably elevated in ADPKD individuals than control subjects. No significant difference between groups regarding Glu298 ASP polymorphisms of eNOS gene was detected. In ADPKD patients, 29 patients (39%) had hypertension, 5 patients (6.7%) had diabetes and 43 patients (57%) had glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 . The polymorphisms of ACE and eNOS genes were not meaningfully different regarding diabetes, high blood pressure, GFR and plasma creatinine in ADPKD individuals (P&gt;0.05). Conclusion: In our study, we could not find any association between polymorphisms of ACE and eNOS genes with renal insufficiency and hypertension in ADPKD patients.

SUN-218 Evaluation of common polymorphisms of eNOS gene and ACE gene in ADPKD patients and their association with HTN and renal failure in ADPKD patients

Autosomal Dominant Polycystic kidney Disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) and generally a late-onset multisystem disorder characterized by: bilateral renal cysts; cysts in multiple cysts in other organs. Renal manifestations include hypertension, renal pain, and renal insufficiency. Risk factors for progressive CKD include: younger age at the diagnosis, large kidney volume (size) on imaging, rapid cyst growth, hypertension, male gender, visible hematuria, and inheritance of a PKD1 versus a PKD2 mutation. The role of Angiotensin Converting Enzyme (ACE) gene polymorphism and endothelial nitric oxide synthase (eNOS) gene polymorphism in the clinical course of ADPKD is not well understood and there is no available index to predict the outcomes and clinical course of ADPKD. Our study evaluated association between these polymorphisms and presence of hypertension and renal failure in ADPKD patients. In this case-control study, 75 ADPKD patients and 100 control wasparticipated. All cases were provided written informed consent 5 cc of whole blood was obtained and transferred to the EDTA solutionand whole bloods was preserved in the temperature of -70◦ c◦ . then all samples of whole blood was referred to the genetic laboratory and DNA was extracted from whole blood by the phenol chloroform extraction and ethanol precipitation techniques. Genotyping for I/D polymorphism in ACE gene and Glu 298 ASP and T 786C polymorphisms in eNOS gene was performed by ARMS- PCR and molecular,s evaluation by special primers for two set genes ; I/D polymorphism in ACE gene and Glu 298 ASP and T 786C polymorphisms in eNOS gene was performed . There were no significant difference between two groups in terms of age and sex. The frequency of DD polymorphism of ACE gene and TC polymorphism of T786C of eNOS were significantly higher in ADPK patients than control but there was no difference in term of Glu 298ASP polymorphisms of eNOS gene. In ADPKD patients, 29 patients (39%) had hypertension, 4 patients (5%) had diabetes, 43 patients (57%) had GFR less than 60mL/min/1.73m2, and 41 patients (55%) had creatinine more than 1.5 mg/mL. The polymorphisms of ACE and eNOS genes were not significantly different in terms of hypertension, diabetes, GFR and creatinine status in ADPKD patients (P>0.05). There was no association between ACE polymorphisms and eNOS gene polymorphisms with renal insufficiency and hypertension in ADPKD patients. It seems that more number of patients need for study on association between polymorphisms and manifestation of ADPKD.

Angiotensin-Converting Enzyme (ACE) D Allele as a Risk Factor for Increase Serum Interleukin-6 and Interleukin-8 in Psoriasis Patients.

BACKGROUND:Psoriasis is a chronic, recurrent inflammatory skin disease. It is characterised by autoimmune, environmental factors and complex genetic disorder.AIM:To explore the role of IL-6, IL-8, and ACE I/D polymorphism in the pathogenesis of Psoriasis and investigation of the relationship between ACE polymorphism and occurrence of psoriasis.PATIENTS AND METHODS:In this study, we took 73 psoriasis patients and 47 healthy patients as a control. These two groups subjected to analysis for ACE gene I/D polymorphism by PCR and biochemical methods.RESULTS:The serum levels of ACE, IL-8 and IL-6 were statistically significantly higher in psoriasis patients compared to healthy subjects (P < 0.001). ID and DD polymorphism were more common in psoriasis patients than healthy subjects. Also, D allele was significantly over-represented in patients compared to controls (52.7% Vs 35.1%).CONCLUSION:ACE gene polymorphism might grant susceptibility to develop psoriasis.

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke

ABSTRACTPurpose: Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke.Method: This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR).Result: In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (β = −0.232, p = 0.024).Conclusion: This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.

Association between risk of type 2 diabetes mellitus and angiotensin-converting enzyme insertion/deletion gene polymorphisms in a Saudi Arabian population.

The link between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the prevalence of type 2 diabetes mellitus (T2DM) developing in the Saudi Arabian population remains controversial. The aim of the present study was to evaluate the association between the ACE I/D gene polymorphism and the risk of developing T2DM and hypertension (HTN) in Saudi Arabian individuals. A total of 220 individuals consisting of 48 control subjects, 70 T2DM, 48 HTN, and 54 T2DM with HTN patients were recruited. Genotyping was performed by polymerase chain reaction initially and mistyping of the DD genotypes was conducted with an insertion-specific primer. The genotyping frequency for the II, ID and DD polymorphism of the ACE gene was 6.8, 42.6 and 48.6% in T2DM patients, 4.2, 50 and 45.8% in HTN patients, 5.6, 55.5 and 38.9% in T2DM patients with HTN and 58.3, 37.5 and 4.2% in control subjects, respectively. The frequency for the D allele was 70% in T2DM patients, 70.8% in HTN patients and 66.7% in T2DM patients with HTN as compared with 22.9% in the control subjects. The genotype and allele frequency of the ACE gene polymorphism varied significantly (P<0.05) in the patients when compared with the control subjects. The current study demonstrated that the ID/DD genotype and the D allele of the ACE gene I/D polymorphism were strongly associated with the risk of T2DM and HTN developing in a Saudi Arabian population.

The association of uncoupling protein 2 (UCP2) exon 8 insertion/deletion polymorphism and ECG derived QRS duration: A cross-sectional study in an Australian rural population

BackgroundAssociations between inherited mitochondrial disease and cardiac conduction have been previously described. However, there are no available studies exploring the mitochondrial uncoupling protein 2 gene (UCP2) insertion/deletion (I/D) polymorphisms interaction on cardiac electrical conduction. Our aim was to determine if ECG-derived QRS duration is associated with UCP2 DD genotype in a cross-sectional Australian aging rural population. MethodsA retrospective study design utilizing a rural health diabetic screening clinic data-base containing observational data from September 2011 to September 2014. Inclusion criteria included were having ECG parameters such as QRS duration measures and a DNA sample within the same subject. Genomic DNA was extracted and subjects were genotyped for the 45-bp I/D polymorphism in the 3′-untranslated region of UCP2. Results281 individuals were available for analysis. On the basis of QRS duration >140ms we found an increased percentage of our population with DD homozygotes, compared to ID heterozygotes and II homozygotes (p=0.047). For other ECG parameters; mean PQ duration, QTc across UCP2 genotypes was not significant (p=NS). QTc using a cut-off >440ms in contingency table analysis revealed no significant differences across UCP2 I/D genotypes. Mean QT dispersion (QTd) was paradoxically less in the UCP2 DD genotype compared to UCP2 II subgroup (p=0.034). DiscussionWe have demonstrated an association between increasing ECG-derived QRS duration >140ms and the UCP2 DD polymorphism. The lack of association with ECG derived QTd and UCP2 DD may suggest that gene-related QRS duration prolongation is independent of cardiac hypertrophy.

Association of ACE Gene I/D polymorphism with migraine in Kashmiri population.

Introduction:Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region.Materials and Methods:The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP).Results:Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene.Conclusion:We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine.

0430: Features of carbohydrate metabolism, cytokines activity and I/D gene ACE polymorphism at patients with arterial hypertension and overweight

The purpose of our research was to study features of carbohydrate metabolism, activation of the pro-inflammatory cytokine-interleukin-18 (IL-18) and anti-inflammatory cytokine-interleukin-10 (IL-10), I/D gene ACE polymorphism at patients with arterial hypertension and overweight.Design and Methods:103 hypertensive patients were examined, which have been divided into 2 groups depending on body mass index (BMI):1st group-24 patients with BMI less than 25, the 2nd group-79 patients with BMI more than 25. The control group - 10 almost healthy subjects. At patients of the 2nd group reliable increase of SBP and DBP is noted-162.5 mmHg and 100.0 mmHg, p<0.05. The analysis of indicators of a carbohydrate exchange showed HbA1c increase at patients of the 1st and 2nd groups in comparison with control-6.97 (3.9-11.6)%, 6.5 (3.7-12.4)% and 5.1 (3.6- 8.1)% respectively, p=.0321.In the 1st group ID genotype-9 patients (35.62%), DD genotype - 13 patients (53.42%); in the 2nd group - ID genotype-37 patients (46.61%), DD genotype-27 patients (30.77%), p=.03821. Besides, at patients of the 2nd group statistically significant increase of level anti-inflammatory IL-10-89.3 (61.3-97.5) pg/ml in comparison with the 1st group and group of control-79.5 (58.8-93.0) pg/ml and 82.0 (58.8-97.5) pg/ml respectively, ρ =.0001 against increase of level pro-inflammatory IL-18 in both groups (173.0 (110.0-210.0) pg/ml 1st group and 176.0 (125.0-205.0) pg/ml- the 2nd group, p =.0001) was noted. The obtained data allow to assume that at patients with arterial hypertension and overweight against prevalence of adverse genotypes of ID and the DD polymorphism of I/D gene ACE polymorphism heavier current of arterial hypertension is observed that is characterized by higher of blood pressure levels and of a carbohydrate metabolism parameters such as HbA1c is noted. Increase of level IL-10 against increase IL-18 at patients with arterial hypertension and overweight, probably, has compensatory character.