Angiotensin-converting Enzyme Variants Research Articles

Single nucleotide polymorphism (SNP) rs4291 of the angiotensin-converting enzyme (ACE) gene is associated with the response to losartan treatment in hypertensive patients.

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the ACE gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of ACE rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of ACE variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of ACE polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12-6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of ACE polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system.

The ACE rs1799752 Variant Is Associated with COVID-19 Severity but Is Independent of Serum ACE Activity in Hospitalized and Recovered Patients.

This paper assesses the association of the insertion/deletion ACE (angiotensin-converting enzyme) variant (rs1799752 I/D) and the serum ACE activity with the severity of COVID-19 as well as its impact on post-COVID-19, and we compare these associations with those for patients with non-COVID-19 respiratory disorders. We studied 1252 patients with COVID-19, 104 subjects recovered from COVID-19, and 74 patients hospitalized with a respiratory disease different from COVID-19. The rs1799752 ACE variant was assessed using TaqMan® Assays. The serum ACE activity was determined using a colorimetric assay. The DD genotype was related to risk for invasive mechanical ventilation (IMV) requirement as an indicator of COVID-19 severity when compared to the frequencies of II + ID genotypes (p = 0.025, OR = 1.428, 95% CI = 1.046-1.949). In addition, this genotype was significantly higher in COVID-19 and post-COVID-19 groups than in the non-COVID-19 subjects. The serum ACE activity levels were lower in the COVID-19 group (22.30 U/L (13.84-32.23 U/L)), which was followed by the non-COVID-19 (27.94 U/L (20.32-53.36 U/L)) and post-COVID-19 subjects (50.00 U/L (42.16-62.25 U/L)). The DD genotype of the rs1799752 ACE variant was associated with the IMV requirement in patients with COVID-19, and low serum ACE activity levels could be related to patients with severe disease.

Influence of sex on renin-angiotensin-aldosterone system metabolites and enzymes in Doberman Pinschers.

Estrogen modulates the renin-angiotensin-aldosterone system (RAAS) in women, but sex differences have not been fully explored in dogs. We hypothesized that the RAAS profile of intact female (IF) Doberman Pinschers (DP) would differ from spayed female (SF) and intact male (IM) DP. Eighteen healthy DP (6 IF, 6 SF, 6 IM). Absolute and indexed RAAS metabolites, angiotensin-converting enzyme (ACE) and ACE2 activities, and genotypes (pyruvate kinase dehydrogenase 4, titin, and ACE variants) were compared among sex groups using Kruskal-Wallis or chi-square tests, and linear regression controlling for age. Data are expressed as median (minimum, maximum) and P < .05 was considered significant. The ACE activity was higher in IF DP (656 pmol/L; 436, 784) compared to SF DP (411 pmol/L; 287, 451; P=.01) and IM DP (365 pmol/L; 276, 1200; P=.04) after controlling for age. Angiotensin II, angiotensin I, and plasma renin activity marker (PRA-S) were higher in IF DP compared to SF DP, but not significantly (P ≤ .25). After controlling for age, angiotensin 1-7/angiotensin I was lower in IF DP compared to SF DP (P=.01). Genotypes did not differ among groups. Most DP (94%) were ACE variant positive. Sex and reproductive status influenced the RAAS of DP, with IF DP showing genotype-independent higher ACE activity. These findings hold implications for sterilization practices in female dogs, and support sex and reproductive status as a source of variability in RAAS studies. Additionally, the frequency of the ACE gene variant was very high in this group of DP.

The Impact of Pharmacogenetics on Pharmacokinetics and Pharmacodynamics in Neonates and Infants: A Systematic Review

In neonates, pharmacogenetics has an additional layer of complexity. This is because in addition to genetic variability in genes that code for proteins relevant to clinical pharmacology, there are rapidly maturational changes in these proteins. Consequently, pharmacotherapy in neonates has unique challenges. To provide a contemporary overview on pharmacogenetics in neonates, we conducted a systematic review to identify, describe and quantify the impact of pharmacogenetics on pharmacokinetics and -dynamics in neonates and infants (PROSPERO, CRD42022302029). The search was performed in Medline, Embase, Web of Science and Cochrane, and was extended by a PubMed search on the ‘top 100 Medicines’ (medicine + newborn/infant + pharmacogen*) prescribed to neonates. Following study selection (including data in infants, PGx related) and quality assessment (Newcastle–Ottawa scale, Joanna Briggs Institute tool), 55/789 records were retained. Retained records relate to metabolizing enzymes involved in phase I [cytochrome P450 (CYP1A2, CYP2A6, CYP2B6, CYP2C8/C9/C18, CYP2C19, CYP2D6, CYP3A5, CYP2E1)], phase II [glutathione-S-transferases, N-acetyl transferases, UDP-glucuronosyl-transferase], transporters [ATP-binding cassette transporters, organic cation transporters], or receptor/post-receptor mechanisms [opioid related receptor and post-receptor mechanisms, tumor necrosis factor, mitogen-activated protein kinase 8, vitamin binding protein diplotypes, corticotrophin-releasing hormone receptor-1, nuclear receptor subfamily-1, vitamin K epoxide reductase complex-1, and angiotensin converting enzyme variants]. Based on the available overview, we conclude that the majority of reported pharmacogenetic studies explore and extrapolate observations already described in older populations. Researchers commonly try to quantify the impact of these polymorphisms in small datasets of neonates or infants. In a next step, pharmacogenetic studies in neonatal life should go beyond confirmation of these associations and explore the impact of pharmacogenetics as a covariate limited to maturation of neonatal life (ie, fetal malformations, breastfeeding or clinical syndromes). The challenge is to identify the specific factors, genetic and non-genetic, that contribute to the best benefit/risk balance.

Severity of coronavirus disease 19: Profile of inflammatory markers and ACE (rs4646994) and ACE2 (rs2285666) gene polymorphisms in Iraqi patients

Susceptibility to coronavirus disease 2019 (COVID-19) and disease severity has recently been associated with inflammatory markers and genetic polymorphisms of ACE (angiotensin-converting enzyme) and ACE2 genes, but the evidence has been inconclusive. This case-control study (99 COVID-19 patients and 96 controls) sought to assess the significance of age, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and SARS-CoV-2 RT-PCR cycle threshold (Ct) in severity of COVID-19. Besides, two variants of ACE and ACE2 genes (rs4646994 and rs2285666, respectively) were analyzed to determine their role in COVID-19 susceptibility and/or disease severity. Results revealed that age, CRP and NLR were significantly elevated in severe cases compared to moderate cases, while RT-PCR Ct value was significantly decreased. Allele and genotypes of both variants were not associated with COVID-19 risk, with the exception of rs2285666 A allele. It showed a significantly higher frequency in female patients than in female controls (probability = 0.041). In conclusion, the study indicated the role of age, CRP, NLR and SARS-CoV-2 RT-PCR Ct in susceptibility to COVID-19 severity. However, analysis of the ACE and ACE2 gene variants (rs4646994 and rs2285666, respectively) showed that the two variants were not associated with the risk of developing COVID-19.

The Association Between Variants of Angiotensin Converting Enzyme (ACE) Gene With Risk Factors in Patients with Ischemic Stroke at Dr. Kariadi Semarang

BACKGROUND : Stroke is the leading cause of death and disability in the world. The occurrence of ischemic stroke is indicated by genetic factors, environmental factors and the interaction between it. Angiotensin Converting Enzyme (ACE) genetic variant is associated with various characteristics of risk factors for ischemic stroke.&#x0D; OBJECTIVE : Identifying genetic variants of Angiotensin Converting Enzyme (ACE) with the Polymerase Chain Reaction (PCR) method and to find it’s correlation beetwen risk factor in patients with Ischemic Stroke at Dr. Kariadi Semarang&#x0D; METHOD : The subjects of the study were 72 patients with ishcemic stroke who were treated at the polyclinic of the Neurology Department Dr. Kariadi Semarang in January - December 2013. DNA extraction of research subjects was carried out at the Laboratory of the Center of Biomedical Research (CEBIOR), Faculty of Medicine, Diponegoro University from January to March 2020. Amplification using the Polymerase Chain Reaction (PCR) method was carried out using an Eppendorf thermocycler. Data were analyzed with SPSS for Windows Version 25&#x0D; RESULT : 72 samples analyzed obtained genetic variants of ACE II 39 (54.2%) samples, genetic variants of ACE DI 30 samples (41.7%), and genetic variants of ACE DD 3 (4.2%) samples. Meanwhile, there was no significant relationship ( p&gt;0,05 ) between genetic variants of ACE and the characteristics of risk factors for ischemic stroke, namely age, gender, Body Mass Index, smoking history, triglyceride levels, HDL levels, LDL levels, obesity and hypertension.&#x0D; CONCLUSION : There are three types of ACE genetic variants, including the ACE II genetic variant, the ACE DI genetic variant, and the ACE DD genetic variant. Among the three genetic variants, ACE II genetic variant is the most common variant and there is no significant relationship to the various risk factor characteristics found in ischemic stroke patients at Dr. Kariadi Gneeral Hospital Semarang.

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

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

Key genetic variants in the renin-angiotensin system and left ventricular mass in a cohort of Polish patients with heart failure.

Heart failure (HF) is a complex disease that is under the control of different physiological systems. Left ventricular mass (LVM) is a strong predictor of HF. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF and LVM. The aim of this study is to examine the association between RAS genetic variants and HF and LVM in the cohort of Polish patients with HF. The study included 401 patients with HF. Two-dimensional M-mode echocardiography was used to assess LVM. Genomic DNA was extracted from blood, and genotyping of the angiotensin-converting enzyme (ACE) (rs4646994), angiotensinogen (AGT) (rs5051), and angiotensin II receptor type 1 (AGTR1) (rs5186) polymorphisms was carried out using polymerase chain reaction (PCR). A significant association was found between HF and the genotypes of G(-6)A AGT, and the homozygotes AA of AGT were significantly less common in the HF vs control group. The results of this study did not confirm the relationship between AGT, ACE and AT1R genetic variants with LVM in Polish patients with HF. Our results suggested that AGT polymorphism may play a protective role in the development of HF.

No credible evidence for links between 2D:4D and COVID-19 outcomes: A probabilistic perspective on digit ratio, ACE variants, and national case fatalities

Research into COVID-19 susceptibility and outcomes are critical, but claims must be carefully evaluated to inform policy decisions. In a recent series of articles, Manning and Fink [1–3] use national-level data to describe associations between case-fatality ratios and male and female finger ratios (2D:4D), a suggested measure of prenatal androgen exposure, as well as angiotensin-converting enzyme (ACE) allele and genotype frequencies. The authors suggest that 2D:4D is linked with ACE variant prevalence, and that higher male 2D:4D is associated with higher case fatality ratios, and point to 2D:4D as a useful prognostic measure for COVID-19 susceptibility. A critical review and robust Bayesian analysis of the hypothesis is described here, finding no conclusive evidence of COVID-19 mortality and 2D:4D, nor associations between 2D:4D and ACE1 allele or ACE2 genotype frequency. This absence of evidence is present for data taken from the second wave of COVID-19 in October 2020. Problematic theoretical grounding, individual-level conclusions drawn from national-level data, and issues with statistical inference in the original articles are discussed. Taken together, the current data offer no clear utility of 2D:4D in determining COVID-19 outcomes.

Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology.

Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology.

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

Association between angiotensin-converting enzyme insertion/deletion polymorphisms and intracranial aneurysm susceptibility: A meta-analysis.

Various studies have evaluated the association between polymorphisms of angiotensin-converting enzyme (ACE) and intracranial aneurysm (IA) risk; however, the results remain inconsistent. The PubMed, Embase, and Wanfang Data databases were systematically searched until January 6th 2016. Case-control studies investigating the association between the ACE polymorphism and IA risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with the fixed or random-effects model assuming allele, homozygote comparison of codominant, heterozygote comparison of codominant, dominant, and recessive models. Seven studies including 1,074 cases and 1,500 controls were included in the current meta-analysis. The results of the analysis indicated that the ACE polymorphism significantly increased IA risk in the allele, homozygote comparison of codominant and dominant models. According to the further stratified analysis by ethnicity, source of control and sample sizes, a significant association was identified between the ACE variant and IA risk in Asian individuals, hospital-based, or large (>300) subgroups in all of the genetic models, not including the recessive model. Furthermore, no significantly increased risk was indicated in Caucasian individuals, population-based, or small (<300) subgroups in the heterozygote comparison of codominant, dominant and recessive models. The available evidence indicates that the ACE polymorphism is associated with an increased risk of IA, particularly in Asian individuals. However, other factors may impact this association. Further large, well-designed multicenter studies are required to validate the findings from the present study.

ACE I/D and MMP-7 A-181G variants and the risk of end stage renal disease.

The variants of angiotensin converting enzyme (ACE) and matrix metalloproteinases (MMPs) genes might be involved in the pathogenesis of end stage renal disease (ESRD) and hypertension. We studied the ACE insertion/deletion (I/D) and MMP-7 A-181G variants in 99 unrelated ESRD patients and 117 individuals without renal complications from Western Iran with Kurdish ethnic background. The frequency of ACE I/D variants was not significantly different between ESRD patients and controls. However, the presence of ACE D allele increased the risk of hypertension in ESRD patients by 2.14-fold (P=0.036). The MMP-7 -181 AG genotype increased the risk of ESRD by 2.04 times (P=0.026). The present study indicated the absence of an association between the ACE I/D polymorphism with the risk of ESRD. However, the ACE D allele increased the risk of hypertension in ESRD patients. Also, the present study suggests a role for MMP-7 AG genotype in the pathogenesis of ESRD.

Abstract TP110: Helicobacter Pylori Infection and Genetic Factors as Determinants of Carotid Plaque Stability

Introduction: Little is known about the role of H pylori in human atherosclerosis. We have previously demonstrated its presence in carotid plaques, especially among asymptomatic patients, with prevalence of cag A-positive strains. Polymorphisms of genes of angiotensin-converting enzyme (ACE), lipoprotein APOE (APOE), IL1 receptor antagonist (IL1Ra) and myeloperoxidase (MPO) are associated with atherosclerosis. We evaluated the role of H pylori in certain features of carotid plaques and assessed allelic and genotypic frequencies and their association with H pylori infection and plaque characteristics. Methods: We studied 137 carotid plaques of patients undergoing endarterectomy. We categorized as stable those predominantly fibrous plaques with scarce inflammatory cells, intact cap and no hemorrhage and unstable those plaques with inflammation, thin cap, ruptured lipid core, thrombi and hemorrhage. We extracted genomic DNA and identified and typified H Pylori DNA. DNA was also obtained from peripheral blood and we identified allelic and genotypic frequencies and susceptibility variants of ACE, APOE, IL1Ra, and MPO genes. Fisher’s exact test (two-tailed) and good fit test were used. Results: There were 72 asymptomatic patients with 47 stable and 25 unstable plaques and 65 symptomatic patients with 13 stable and 52 unstable plaques (p&lt;0.0001). H pylori infection was present in 48 of 60 stable plaques and 31 of 77 unstable plaques (p&lt;0.0001). In addition, stable infected plaques more often carried the more virulent cag A strain. H pylori cag A-negative plaques had larger intima media complex thickness than cag A-positive and H pylori -negative plaques. Stable infected plaques were associated to alleles APOE-33 and IL1RN-11. Unstable noninfected plaques were associated to proatherogenic alleles ACE-DD, APOE*4, APOE*2, IL1RN*2, and MPO-GG. Conclusions: Histopathological features of plaque instability are associated to the presence of recent symptoms. H pylor i infection with the virulent cag A strain is highly prevalent in stable carotid plaques of asymptomatic subjects. Noninflammatory genotypes are present in stable infected plaques whereas proatherogenic polymorphisms are predominant in unstable noninfected plaques.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients.

AIMTo investigate the role of genetic variants of angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy (DN) patients.METHODSIn the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor (ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio (ACR) in urine. Genotyping of ACE I/D and AGT M235T polymorphisms were performed by using primer specific polymerase chain reaction (PCR) and PCR-RFLP techniques, respectively.RESULTSForty-eight percent of DN patients (responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric (≥ 30 and < 300 mg/g creatinine) or macro-albuminuric (≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients (55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response (72%).CONCLUSIONACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235T polymorphisms.

Insertion/deletion gene variants of angiotensin converting enzyme do not predispose cameroonians of the Bantu ethnic group to essential hypertension

The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene has been reported to be implicated in the predisposition to essential hypertension (EH). This association may depend on ethnic and genetic backgrounds. The objective of this study was to determine if the possible I/D polymorphism in the Bantu ethnic group of Cameroon is associated with EH. Data were analyzed from 60 patients and 50 healthy controls in order to access the risk factors of EH in this ethnic group. Comparison of gene and allele frequency distributions between the two populations revealed that systolic and diastolic blood pressures, age, family history and lack of physical exercise were risk factors of EH in this ethnic group. Comparison of means of age, systolic and diastolic blood pressures as well as the proportions of individuals with a family history of EH and lack of physical exercise were higher in the hypertensive than the normotensive group (p 0.05). Moreover, analyses of relationship between ACE I/D gene variants and EH did not reveal any association (p > 0.05). Consistently, the two groups also did not present with differences in I and D allele distribution (p > 0.05). These results suggest that EH is not associated with ACE I/D polymorphism. © 2016 International Formulae Group. All rights reserved. Keywords: ACE, Gene polymorphism, SWR, Cameroon

Genotypes of the renin-angiotensin system and glucocorticoid complications.

Angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) are recognized as important regulators of body mass index (BMI) and systemic blood pressure (BP). An association between these single nucleotide polymorphisms (SNP) of AGT and ACE genes and obesity or hypertension has been established. This study examined relationships between the molecular variants of the AGT and ACE genes and bodyweight or BP in children treated with glucocorticoids for nephrotic syndrome. Twenty Japanese children (male, n = 14; female, n = 6; age, 2-13 years) were genotyped for AGT polymorphisms (M235T and A-6G) and the ACE polymorphisms (insertion/deletion: I/D and rs4341). All of the children studied were treated with daily prednisolone 2 mg/kg for 4 weeks and thereafter alternate-day prednisolone for 8 weeks. BMI, BMI z-scores, blood lipids, renal function and BP in each group were evaluated during the study period. BMI and BMI z-scores during the glucocorticoid therapy were significantly higher in the TT genotype of the AGT M235T polymorphisms and the AA genotype of the AGT A-6G polymorphisms compared to other genotypes (P < 0.05). In contrast, the molecular variant of ACE I/D and rs4341 genotypes did not change bodyweight during the glucocorticoid exposure. It was evident, however, that the BP and blood lipids and renal function were not significantly influenced by the AGT and ACE polymorphisms. The TT genotype of the AGT M235T and the AA genotype of the A-6G polymorphisms may predispose children to bodyweight gain when initially treated with glucocorticoids for nephrotic syndrome.

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

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

Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort

Hypertrophic cardiomyopathy is an autosomal dominant disorder, characterized by thickening of the myocardium with a variable clinical course. Mutations in 14 sarcomeric genes have been implicated resulting in phenotypic and genotypic heterogeneity. The phenotypic expression of HCM is not only determined by the sarcomeric gene mutations but the genetic predilection of an individual also account for the inter-individual variability and genes with such functional variants that affect phenotypic expression are referred to as Modifier genes. Hence genetic variants of Angiotensin converting enzyme (ACE-2), Tumor necrosis factor- alpha (TNF-α) and Heat shock protein -70 (HSP70) genes have been considered in the present study to understand their role as modifiers of HCM. The study was carried out by Genotyping of 100 HCM and 100 controls by Polymerase chain reaction based restriction fragment length polymorphism analysis. The present study revealed a significant association of the HSP70-1 and HSP70-2 polymorphisms while ACE-2 and TNF-α genes were found to be statistically insignificant. However patients with the rare/variant genotypes were observed to have stronger clinical manifestations and echocardiographic parameters. This was further confirmed by Linkage disquillibrium analysis wherein individuals with the haplotypes GCGC and GCGT seemed to have increased susceptibility to HCM. The MDR analysis revealed a synergistic interaction of TNF-α with ACE-2 and HSP70 polymorphisms indicating their modifying effect in the presence of other environmental factors. Hence the present study emphasized the role of ACE-2, TNF-α and HSP70 polymorphisms as modifiers of the phenotypic expression in conjunction with other sarcoemric mutations and single nucleotide variations.

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

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