Renin-angiotensin System Gene Polymorphisms Research Articles

Angiotensin-converting enzyme I/D gene polymorphism and risk of type 2 diabetes mellitus in Iranian individuals

This study aimed to examine the relationship between type 2 diabetes mellitus (T2DM) and renin-angiotensin system gene polymorphisms in the Iranian population. Additionally, we performed a straightforward meta-analysis of the present articles to better understand this role. A total of 100 Iranian individuals, 50 patients with T2DM, and 50 age-matched healthy individuals were included in this study. DNA was extracted using the salting-out approach, polymerase chain reaction was used to amplify the angiotensin-converting enzyme (ACE) gene, electrophoresis techniques were used, and genotyping was performed. We also searched PubMed, Web of Science, Scopus, and Google Scholar databases for papers published in 2023. We found a significantly higher frequency of I/D genotype in the patient group than in the control group, and the risk of T2DM was 10 times higher in individuals with the I/D genotype (OR, 10 [95% CI, 3.7 to 27]; p < 0.0001) and also 2.85 time higher in individuals with the D allele OR, 2.85 [95% CI, 1.55 to 5.24]; p < 0.001). The ACE polymorphism alleles D and I/D genotypes may increase the risk of developing T2DM in an Iranian population.

Renin-angiotensin system gene polymorphism and aging

A personalized healthy aging program, aimed at preservation of functional capacities in old ages, should consider genetic (hereditary) factors that determine the structure and functions of body organs and systems, and their age-related changes. Individual genetic characteristics of a person can influence the aging process. For this reason, recent research focuses on identifying genetic mechanisms of aging and longevity associated with multifactorial diseases. Renin-angiotensin system (RAS) contributes to the development of pathological conditions leading to cardiovascular diseases, cognitive changes, disorders of auditory and visual analyzers, and may determine the preservation of functional capacities in older adults. We present a literature review of the role of the RAS gene polymorphisms in the aging processes. The results of the synthesis of Russian and international literature indicated the contribution of polymorphic variants of the angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II receptor type 1 (AGTR1) genes to the development of pathological conditions and the associated decreases in functional capacities of an elderly person. Testing for these polymorphisms can be of a practical importance for personified health assessment and development of timely preventive interventions aimed at improving life expectancy and quality of life among older adults.

Genetic Variations of Angiotensinogen, Angiotensin Converting Enzyme, and Angiotensin Type 1 Receptor with the Risk of Pulmonary Tuberculosis.

There is little data regarding the impact of renin-angiotensin system (RAS) gene polymorphisms on tuberculosis. The current study designed to survey the possible association between RAS polymorphisms and the risk of pulmonary tuberculosis (PTB) in a sample of the southeast Iranian population. This case-control study was done on 170 PTB patients and 170 healthy subjects. The AGT rs699 C&gt;T, ACE rs4341 C&gt;G and AT1R rs5186 C&gt;A variants were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and ACE rs4646994 (287bp I/D) variant by PCR method. Regarding AT1R rs5186 A&gt;C polymorphism, the findings revealed that AC genotype and C allele significantly decreased the risk of PTB (OR=0.39, 95% CI=0.22-0.67, p=0.001, and OR=0.53, 95% CI=0.25-0.72, p=0.002, C vs. A, respectively). The TC genotype and C allele of AGT rs699 T&gt;C significantly associated with decreased the risk of PTB (OR=0.45, 95% CI=0.28-0.74, p=0.002, TC vs. TT and OR=0.51, 95% CI=0.32-0.80, p=0.005, C vs. T, respectively). The ID genotype of ACE 287bp I/D significantly increased the risk of PTB (OR=1.88, 95% CI=1.12-3.17, p=0.017). Our finding did not support an association between ACE rs4341 C&gt;G variant and the risk of PTB. In summary, the findings revealed an association between AT1R rs5186 A&gt;C, AGT rs699 T&gt;C and ACE 287bp I/D polymorphisms and the risk of PTB in a sample of the southeast Iranian population. Further investigation with higher sample sizes and diverse ethnicities are required to confirm our findings.

Genetic Association of Angiotensin-converting enzyme 2 ACE-2 (rs2285666) Polymorphism with the Susceptibility of COVID-19 Disease in Iraqi Patients

Significant risks to human health are posed by the 2019 coronavirus illness (COVID-19). SARS coronavirus type 2 receptor, also known as the major enzyme in the renin-angiotensin system (RAS), angiotensin-converting enzyme 2 (ACE-2), connects COVID-19 and RAS. This study was conducted with the intention of determining whether or not RAS gene polymorphisms and ACE-2 (G8790A) play a part in the process of predicting susceptibility to infection with COVID-19. In this study 127 participants, 67 of whom were deemed by a physician to be in a severe state of illness, and 60 of whom were categorized as "healthy controls" .The genetic study included an extraction of genomic DNA from blood samples of each covid 19 patients and healthy controls, then amplification the site of SNP (rs2285666) Within the ACE2 gene by using specific primers, sequencing PCR products, and genotyping to detect the role of the ACE-2 gene (rs2285666) in the incidence of COVID-19. ACE-2 (rs2285666) is statistically associated to COVID-19. The COVID-19 group had 65.67 %of individuals with the wild-type homozygous genotype (GG) and 20% in the control group, while the control group had 63.33% of individuals with the mutant genotype (AA). Consequently, the wild-type homozygous (GG) and allele (G) may be considered a risk factor (etiological fraction E. F) for COVID-19 in Iraqi patients, whereas the mutant homozygous (AA) and allele (A) may be considered a protective factor (preventive fraction). The findings of the present study reveal that carriers of the GG genotype of ACE2 (rs2285666) are substantially more susceptible to COVID-19.

SNPs of ACE1 (rs4343) and ACE2 (rs2285666) genes are linked to SARS-CoV-2 infection but not with the severity of disease

COVID-19 and the renin-angiotensin system (RAS) are linked by angiotensin-converting enzyme 2 (ACE2), a key enzyme in RAS that has been validated as a SARS-CoV-2 receptor. Functional ACE1/ACE2 gene polymorphisms may lead to the imbalance between ACE/ACE2 ratio and thus generating RAS imbalance that is associated with higher degrees of lung damage in ARDS that may contribute to the COVID-19 infection outcome. Herein, we investigated the role of RAS gene polymorphisms, ACE1 (A2350G) and ACE2 (G8790A) as risk predictors for susceptibility and severity of COVID-19 infection. A total of 129 included: negative controls without a history of COVID-19 infection (n = 50), positive controls with a history of COVID-19 infection who were not hospitalized (n = 35), and patients with severe COVID-19 infection who were hospitalized in the intensive care unit (n = 44). rs4343 of ACE and rs2285666 of ACE2 were genotyped using PCR–RFLP method. Our results indicated that susceptibility to COVID-19 infection was associated with age, GG genotype of A2350G (Pa = 0.01; OR 4.7; 95% CI 1.4–15.1 and Pc = 0.040; OR 2.5; 95% CI 1.05–6.3) and GG genotype of G8790A (Pa = 0.044; OR 6.17; 95% CI 1.05–35.71 and Pc = 0.0001; OR 5.5; 95% CI 2.4–12.4). The G allele of A2350G (Pa = 0.21; OR 1.74; 95% CI 0.73–4.17 and Pc = 0.007; OR 2.1; 95% CI 1.2–3.5) and G allele of G8790A (Pa = 0.002; OR 4.26; 95% CI 1.7–10.65 and Pc = 0.0001; OR 4.7; 95% CI 2.4–9.2) were more frequent in ICU-admitted patients and positive control group. Also lung involvement due to COVID-19 infection was associated with age and the comorbidities such as diabetes. In conclusion, our findings support the association between the wild genotype (GG) of ACE2 and homozygote genotype (GG) of ACE1 and sensitivity to COVID-19 infection, but not its severity. However, confirmation of this hypothesis requires further studies with more participants.

Risk Assessment Using the Association Between Renin-Angiotensin Genes Polymorphisms and Coronary Artery Disease.

Coronary artery disease (CAD) is a multifactorial disease that involves genetic and environmental interaction. In addition to the well-known CAD risk factors, such as diabetes mellitus, hypertension, hyperlipidemia, and atherosclerosis, it has a genetic component that predisposes to its occurrence even in young people. One of the most commonly studied genes that increase the susceptibility to CAD is renin-angiotensin system (RAS) genes polymorphisms mainly angiotensin-converting enzyme gene (ACE) polymorphisms, angiotensinogen polymorphisms, angiotensin- II type 1 receptor gene polymorphisms, and many other genes. These genetic polymorphisms have a direct association with CAD development or indirect association through causing atherosclerosis and hypertension which, in turn, are complicated by CAD later on. The difference between genetic mutations and polymorphisms lies in the frequency of the abnormal genotype. If the frequency is 1% and more in the general population, it is called polymorphism and if it is less than 1%, then it is called a mutation.According to our findings, after thorough searching, which support the association of RAS genes polymorphisms with premature CAD, hypertension, hypertrophic cardiomyopathy, and atherosclerosis, we recommend additional studies in the form of clinical trials and meta-analyses aiming to create a specific diagnostic tool for CAD risk assessment and discovering the high-risk people as early as possible. Targeted gene therapy, being the future of medicine, needs to be taken into researchers' consideration. It can have promising results in these cases.

The role of the renin-angiotensin system gene polymorphisms in the development of carbohydrate disorders in patients with arterial hypertension

Arterial hypertension and type 2 diabetes mellitus are the most widespread comorbid pathologies. The coexistence of these disorders accelerates the development of micro- and macrovascular complications, considerably increases the cardiovascular risk, as well as the risk of stroke and end stage renal disease. The synergism of these two pathologies is caused by the unity of pathogenetic mechanisms. Genetic predisposition also contributes to the development of both pathologies. It is well known that blockade of the renin-angiotensin system slows down the development of type 2 diabetes mellitus and also reduces the frequency of cardiovascular or kidney events in patients with these disorders. Gene polymorphisms of the reninangiotensin system are thoughtfully studied in the context of cardiovascular disease development. Currently, the role of gene polymorphisms in the development of carbohydrate disorders is not established, however, there is a high probability of their influence and importance. The purpose of review is to analyze the accumulated data on the effects of the renin-angiotensin system gene polymorphisms on the development of arterial hypertension and type 2 diabetes mellitus.

Renin–angiotensin system gene polymorphisms and colorectal cancer risk: a meta-analysis

Objective:The renin–angiotensin system gene has been implicated in the progression of colorectal cancer. Nevertheless, the details of that role remain controversial. We performed a meta-analysis to investigate the correlation between renin–angiotensin system gene polymorphisms and colorectal cancer.Methods:We retrieved relevant studies from PubMed and Embase. Subsequently, fixed or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs).Results:We identified six studies of the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism, and two studies of the angiotensinogen M235T polymorphism. The angiotensin-converting enzyme I/D polymorphism did not significantly correlate with colorectal cancer risk in the total population (DD vs. II: OR 0.77, 95% CI 0.39–1.50; DI vs. II: OR 1.05, 95% CI 0.85–1.30; dominant model: OR 0.94, 95% CI 0.68–1.31; recessive model: OR 1.01, 95% CI 0.80–1.27). Similarly, the angiotensinogen M235T polymorphism was not associated with colorectal cancer risk (TT vs. MM: OR 1.38, 95% CI 0.52–3.67; TM vs. MM: OR 1.19, 95% CI 0.96–1.47; dominant model: OR 1.28, 95% CI 0.77–2.14; recessive model: OR 1.17, 95% CI 0.53–2.59).Conclusion:Our findings suggest that the angiotensin-converting enzyme I/D and angiotensinogen M235T polymorphisms are unlikely to correlate with colorectal cancer.

Effects of Angiotensin Converting Enzyme Polymorphism in Acute Myocardial Infarction

It has been established that renin angiotensin system gene polymorphism, such as angiotensin converting enzyme (ACE), could contribute to a higher occurrence of acute myocardial infarction (AMI). Thus, the objective of this study was to evaluate the effects of the variation of the number of copies of the ACE gene in the AMI. Adult mice, genetically modified to express different concentrations of the ACE were used (one, two and three copies – ACE 1, ACE 2 and ACE 3). The animals were divided into 9 groups (n = 10): 3 without AMI ‐ ACE 1, ACE 2 and ACE 3; 3 infarcted groups assessed 7 days after AMI ‐ ACE 1‐MI7, ACE 2‐MI7 and ACE 3‐MI7; 3 infarcted groups assessed 28 days after AMI ‐ ACE 1‐MI28, ACE 2‐MI28 and ACE 3‐MI28. Infarcted animals were submitted to AMI by ligature of the left coronary artery. Cardiac function by echocardiography, heart rate variability (HRV) and baroreflex sensitivity were evaluated. Regarding the echocardiographic data, the E/A ratio was higher in the ACE group 3‐MI7 than in the non‐infarcted groups with one and two copies of ACE and higher than in the infarcted group with two copies of the ACE gene (ACE 3‐MI7: 3.47 ± 0.50 vs. ACE 1: 1.08 ± 0.14, ACE 2: 1.24 ± 0.16 and ACE 2‐MI7: 1.74 ± 0.25); the fractional area change was lower in the infarcted groups ACE 1‐MI7, ACE 2‐MI7 and ACE 3‐MI7 compared to non‐infarcted and was lower in the ACE group 3‐MI7 than in the ACE groups 2‐MI7 and ACE 1‐MI7 (ACE 3‐MI7: 21,30 ± 1,47 vs. ACE 1‐MI7: 30,10 ± 1,80 and ACE 2‐MI7: 31,12 ± 1,47%). Regarding the autonomic parameters sympathetic modulation was higher in the ACE group 3‐MI7 than in the ACE 1, ACE 2 and ACE 1‐MI7 groups (ACE 3‐MI7: 14.85 ± 2.36 vs. ACE 1: 4.76 ± 2.00, ACE 2: 4.34 ± 1.40 and ACE 1‐MI7: 5.13 ± 1.88 ms2); and the sympatovagal balance was higher in the ACE group 3‐MI7 than in the ACE group 1‐MI7 (ACE 3‐MI7: 2.22 ± 0.17 vs. ACE 1‐MI7: 0.81 ± 0.25). When comparing infarcted groups 7 and 28 days after AMI, it was observed that the baroreflex efficiency index was higher in the ACE group 1‐MI28 than in the infarcted groups assessed 7 days after the infarction (ACE 1‐MI28: 0.28 ± 0.03 vs. ACE 1‐MI7: 0.15 ± 0.02, ACE 2‐MI7: 0.17 ± 0.01 and ACE 3‐MI7: 0.17 ± 0.01). Infarcted animals with 3 copies of the ACE gene had lower survival (41%) and animals with 1 copy of the ACE gene had greater survival (71%) at the end of the study.CONCLUSIONOur results of cardiac function, cardiovascular autonomic function and survival curve indicate that animals with three copies of the ACE gene presented a worse evolution after myocardial infarction in relation to the animals with one copy of the ACE gene.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Association of renin-angiotensin system genes polymorphisms and risk of premature ST elevation myocardial infarction in young Mexican population.

: The renin-angiotensin system plays an important role in the regulation of blood pressure and the development of coronary artery disease. The aim was to examine the association of the insertion deletion in the angiotensin-converting enzyme gene, M235T and T174M polymorphisms in the angiotensinogen gene with ST elevation acute myocardial infarction (STEAMI) in young Mexican population. We analyzed 242 unrelated patients with STEAMI 45 or less years of age, admitted to a cardiovascular intense care unit, and 242 individuals without STEAMI matched by age and sex, recruited from January 2006 and June 2013. The polymorphisms insertion deletion, M235T and T174M were determined in all participants by a polymerase chain-reaction-restriction fragment length polymorphism assay. There was a significant difference in the insertion deletion genotype distribution between two groups (P = 0.03) and a higher percentage of the T allele M235T polymorphism in the group of STEAMI patients (P = 0.02). The T174M polymorphism was not associated (P = 0.08). The insertion deletion and M235T polymorphisms, smoking, hypertension, familial history of cardiovascular disease and dyslipidemia were independent risk factors for STEAMI. Our results identified that the D allele from the insertion deletion and M235T but not T174M polymorphisms represent an independent risk factor for STEAMI in young Mexican population.

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.

The relationship between ACE/AGT gene polymorphisms and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes.

Aims:This study aims to investigate the association between renin-angiotensin system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes.Methods:We consecutively included 1491 patients for the assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146 patients without retinopathy (DNR). Albuminuria was defined by urine albumin creatinine ratio and albumin excretion rate.Results:Compared with the NDR patients, the DR cases displayed a higher proportion of diabetic nephropathy (32.68% vs. 6.52%, χ2 = 150.713, p < 0.001). The DR cases and DNR individuals did not differ in the frequency of genotypes and alleles of ACE I/D and AGT M/T (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of DD (χ2 = 4.181, p = 0.041), but no significant difference exists in the other stratified BMI and hypertension analyses (all p > 0.05). Binary logistic regression displays that the association of the ACE and AGT gene polymorphisms in DR patients is not significant after adjusting for confounding covariates in all the comparisons.Conclusions:The ACE and AGT gene polymorphisms are not associated with the progress of diabetes developing into retinopathy in Chinese patients with type 2 diabetes. However, more investigations are needed to further prove the association.

Family history and renin-angiotensin system gene polymorphisms in Chinese patients with type 2 diabetes mellitus.

A positive family history is recognized as an important risk factor for type 2 diabetes mellitus (T2DM), but the association of family history with rennin-angiotensin system (RAS) gene polymorphisms has not been reported yet, thus we aim to investigate it.Family history records, clinical and biochemical data were obtained from 1239 T2DM patients. Polymerase chain reaction (PCR) was performed for angiotensin-converting enzyme (ACE) genotyping and PCR-restricted fragment length polymorphism was used for angiotensinogen (AGT) genotyping.Patients with a negative family history had higher level of triglyceride and blood pressure, whereas those with a positive family history showed younger onset age and lower body mass index value (All P < .05), these findings were age-dependent. The percentage of hypertension was lower with a higher percentage of overweight among the patients with a positive family history (All P < .05). Patients with a positive family history and those with a negative family history had comparable genotype and allele distribution of ACE gene insertion/deletion polymorphisms and AGT gene M/T polymorphisms.A positive family history of diabetes was not associated with the RAS gene polymorphisms.

Angiotensin II receptor type 1 A1166C modifies the association between angiotensinogen M235T and chronic kidney disease.

Single nucleotide polymorphisms (SNPs) in renin-angiotensin system (RAS) genes are associated with RAS imbalance and chronic kidney disease (CKD). We performed a case-control study and meta-analysis to investigate the association between angiotensinogen (AGT) M235T polymorphism and CKD. A total of 634 patients with end-stage renal disease and 739 healthy controls were studied. We also searched PubMed and the Cochrane Library to identify prospective observational studies published before December 2015. We found that the TT and MT genotypes were associated with a higher risk of CKD than the MM genotype (odds ratio [OR]: 3.56; 95% confidence interval [CI]: 1.14–11.16 and OR: 2.93; 95% CI: 0.91–9.46, respectively). Thirty-eight study populations were included in the meta-analysis. The T allele was associated with a higher risk of CKD than the M allele in all populations (OR: 1.19; 95% CI: 1.08–1.32). The OR was 1.33 in Asians (95% CI: 1.06–1.67) and 1.10 in Caucasians (95% CI: 1.02–1.18). Evaluation of gene-gene and gene-environment interactions using epistasis analysis revealed an interaction between AGT M235T and angiotensin II receptor type 1 A1166C in CKD (OR: 0.767; 95% CI: 0.609–0.965). Genetic testing for CKD in high-risk individuals may be an effective strategy for CKD prevention.

Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents

BackgroundEpidemiological studies have demonstrated the influence of environmental factors on HBP in the population of Lithuanian children, although the role of genetic factors in hypertension has not yet been studied. The aim of this study was to assess the distribution of AGTR1, AGT, and ACE genotypes in the Lithuanian child population and to determine whether these genotypes have an impact on HBP in childhood.MethodsThis cross-sectional study enrolled 709 participants aged 12–15 years. The subjects were genotyped for AGT (M235 T, rs699), AGTR1 (A1166C, rs5186), and ACE (rs4340) gene polymorphisms using real-time and conventional polymerase chain reactions. Blood pressure and anthropometric parameters were measured.ResultsThe prevalence of HBP was 38.6% and was more frequently detected in boys than in girls (47.9% vs. 29.5%; p < 0.001). No significant differences in the frequencies of the AGT or AGTR1 genotypes or alleles between boys and girls were observed, except for ACE genotypes. The mean SBP value was higher in HBP subjects with ACE ID genotype compared to those with ACE II homozygotes (p = 0.04). No significant differences in BP between different AGT and AGTR1 genotype groups were found. Boys who carried the ACE ID + DD genotypes had higher odds of having HBP than carriers of the ACE II genotype did (controlling for the body mass index (BMI): ORMH = 1.83; 95% CI, 1.11–3.02, p = 0.024; and controlling for waist circumference (WC): ORMH = 1.76; 95% CI, 1.07–2.92, p = 0.035). These associations were not significant among girls. The same trend was observed in the multivariate analysis – after adjustment for BMI and WC, only boys with ACE ID genotype and ACE ID + DD genotypes had statistically significantly increased odds of HBP (aOR = 2.05; 95% CI, 1.19–3.53 (p = 0.01) and aOR = 1.82; 95% CI, 1.09–3.04 (p = 0.022), respectively).ConclusionsThe evaluated polymorphisms of the AGT and AGTR1 genes did not contribute to the presence of HBP in the present study and may be seen as predisposing factors, while ACE ID genotypes were associated with significantly increased odds for the development of HBP in the Lithuanian child and adolescent population - especially in boys.

Renin-angiotensin system gene polymorphisms as potential modifiers of hypertrophic and dilated cardiomyopathy phenotypes.

The renin-angiotensin (RAS) pathway has an important role in the etiology of heart failure and given the importance of RAS as a therapeutic target in various cardiomyopathies, genetic polymorphisms in the RAS genes may modulate the risk and severity of disease in cardiomyopathy patients. In the present study, we examined the association of RAS pathway gene polymorphisms, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin receptor type 1 (AGTR1) with risk and disease severity in Asian Indian idiopathic cardiomyopathy patients. The case-control study was conducted in 400 cardiomyopathy patients diagnosed with HCM, DCM, or restrictive cardiomyopathy (RCM) and 235 healthy controls. Genotyping of patients and controls was done by PCR-RFLP assays. Left ventricular wall thickness and left ventricular ejection fraction were measured by means of M-mode echocardiography. We observed significantly higher prevalence of ACE DD and AGTR1 1166CC genotypes in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) patients. Also, 235TT genotype of AGT (M235T) was significantly associated with enhanced risk of the disease phenotype in HCM, DCM, and RCM.

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

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

Роль полиморфизмов генов системы ренин‑ангиотензин в этиологии ранней и поздней преэклампсии

Роль полиморфизмов генов системы ренин‑ангиотензин в этиологии ранней и поздней преэклампсии

Atrial flutter/fibrillation in patients receiving transcatheter closure of atrial septal defect.

Atrial flutter/fibrillation (AFL/Af) is a common late complication in atrial septal defect (ASD) patients even after occluder implantation. We try to delineate the risk factors of persistent AFL/Af. From 1998 to 2010, all patients older than 18years of age who received ASD occluder implantation in our hospital were enrolled, and their records were retrospectively reviewed. In addition, renin-angiotensin system gene polymorphisms including angiotensinogen gene, A1166C polymorphism on the angiotensin II type I receptor gene, and insertion/deletion (I/D) patterns on the angiotensin-converting enzyme gene were checked using direct sequencing. A total of 517 patients (male/female 127/390) were enrolled. The mean age of patients receiving occluder deployment was 41.5±14.5years. Prior to occluder deployment, 3.9% of patients had persistent Af, 3.1% of patients had paroxysmal Af, and 0.8% had AFL. After a follow-up of 1894 patient-years, 3.5% had persistent Af and 1.9% of patients had paroxysmal Af. The greatest risk factors of AFL/Af genesis included age, occluder size, presence of multiple ASDs, and underlying thyroid or mitral valve disorder (p<0.001, p<0.001, p=0.033, p=0.016, and p=0.012, respectively). Preoperative AFL/Af status is the most important factor in determining AFL/Af resolution and progression after an intervention. The renin-angiotensin system gene polymorphisms had no association with AFL/Af genesis, and progression or resolution after intervention. AFL/Af is common after ASD occluder implantation, and predisposed by older age, larger and multiple ASDs, and underlying disorders. Preoperative atrial arrhythmia status is the most important predictor of AFL/Af progression or resolution. Renin-angiotensin system gene polymorphisms had no association with AFL/Af.

Renin-angiotensin system gene polymorphisms and endometrial cancer.

Endometrial cancer (EC) is the most common gynaecological malignancy and its incidence is increasing. Dysregulation of the endometrial renin–angiotensin system (RAS) could predispose to EC; therefore, we studied the prevalence of RAS single nucleotide polymorphisms (SNPs) in Australian women with EC. SNPs assessed were AGT M235T (rs699); AGTR1 A1166C (rs5186); ACE A240T and T93C (rs4291, rs4292) and ATP6AP2 (rs2968915). They were identified using TaqMan SNP Genotyping Assays. The C allele of the AGTR1 SNP (rs5186) was more prevalent in women with EC (odds ratio (OR) 1.7, 95% confidence interval (CI) (1.2–2.3), P=0.002). The CC genotype of this SNP is associated with upregulation of the angiotensin II type 1 receptor (AGTR1). The G allele of AGT rs699, which is associated with higher angiotensinogen (AGT) levels, was less prevalent in women with EC (OR 0.54, 95% CI (0.39–0.74), P<0.001) compared with controls. AGT and AGT formed by removal of angiotensin I (des(Ang I)AGT) are both anti-angiogenic. In women with EC who had had hormone replacement therapy (HRT), the prevalence of the AGTR1 SNP (rs5186) and the ACE SNPs (rs4291 and rs4292) was greater than in women who had no record of HRT; SNP rs4291 is associated with increased plasma ACE activity. These data suggest there is an interaction between genotype, oestrogen replacement therapy and EC. In conclusion, the prevalence of two SNPs that enhance RAS activity was different in women with EC compared with healthy controls. These genetic factors may interact with obesity and hyperoestrogenism, predisposing ageing, obese women to EC.