Angiotensinogen Gene M235T Research Articles

Association between angiotensinogen M235T gene polymorphism and risk of ischemic stroke among the Ethiopian population: a case control study

Ischemic stroke (IS) is a multifaceted, complicated illness resulting from a confluence of genetic, environmental and vascular risk factors. Many genes that may contribute to ischemic stroke have been discovered in humans. The genetic contribution appears to be greater in IS patients with hypertension. There is conflicting evidence about a positive correlation between the AGT M235T polymorphism and ischemic stroke. The aim of this study was to examine the possible association of the AGT M235T gene polymorphism with the risk of ischemic stroke. A hospital-based case-control study was carried out in 36 ischemic stroke patient cases and 36 age- and sex-matched healthy controls. Clinical parameters were measured to assess the associated risk factors. DNA was isolated from blood samples, and the AGT M235T genotypes were identified using polymerase chain reaction (PCR) and analyzed by agarose gel electrophoresis. The AGT-TT genotype (OR = 4.64, 95% CL = 1.23–17.4; p = 0.023 and T allele (OR = 2.54, 95% CL = 1.28–5.02; p = 0.003) were significantly more common in patients than in controls, indicating that it may be a major risk factor for the development of ischemic stroke. The results suggest that there may be a significant correlation between the AGT M235T gene polymorphism and the development of ischemic stroke in the studied Ethiopian population.

Angiotensinogen Gene M235T and T174M Polymorphisms in Diabetic Nephropathy in a Bangladeshi Population

Background: Marker gene polymorphisms linked with the renin-angiotensin-aldosterone system (RAAS) have been broadly studied in diabetic nephropathy (DN) patients considering that RAAS is a potential drug target to slow down kidney disease progression. Objectives: The aim of the present study was to determine the link between M235T and T174M variants of angiotensinogen (AGT) gene and DN. Methods: A total of 93 patients with DN, mean age of 56±8 years, systolic blood pressure (SBP) of 141±14, and diastolic blood pressure (DBP) of 84±7 mm Hg (mean±SD) were investigated, among whom 59 patients had a family history of type 2 diabetes mellitus. A total of 96 healthy subjects served as the control group with no family history of diabetic nephropathy (FHDN) and type 2 diabetes mellitus, a mean age of 47±10 years, SBP of 126±11, and DBP of 76±6 mm Hg. PCR–restriction fragment length polymorphism was employed for genotyping M235T and T174M molecular variants. Results: Genotype frequencies of the variants M235T (χ2=2.038, P=0.361) and T174M (χ2=2.952, P=0.229) did not show any statistically significant association with type 2 diabetic nephropathy (T2DN) compared to the control. Based on FHDN and family history of diabetes mellitus (FHDM), the frequency of genotypes of M235T marker (P=0.360) in FHDN, and (P=0.886) FHDM; T174M marker (P=0.641) in FHDN, and (P=0.425) FHDM also did not show any statistically significant association with T2DN compared to the controls. Conclusion: M235T and T174M variants were not associated with DN in a Bangladeshi population.

The Association of Angiotensin-converting Enzyme I/D and Angiotensinogen M235T Polymorphism Genes with Essential Hypertension: A Meta-analysis

Objective: Essential or primary hypertension in developing countries has become a major problem. Recent hypertension-related research has revealed susceptibility genes in genome-wide association studies. Several studies have associated angiotensin converting enzyme (ACE) I/D and angiotensinogen (AGT) M235T polymorphisms with essential hypertension, but results have been inconsistent. This meta-analysis aimed to clarify the association of AGT and ACE polymorphisms with the risk of primary hypertension.
 Methods: PubMed, Embase database, Medline, Goggle Scholar, Scopus.com, as well portal Garuda (www.garuda.ristekdikti.go.id) and Cochrane were used to retrieve all publications from 2006-2020 relating risk factors for hypertension with ACE I/D and AGT M235T polymorphisms. The meta-analysis was conducted from January –April 2020. All association studies were identified and data extracted from each study. Revman 5.3 software was used for meta-analysis to estimate odds ratios (OR) after extracting data and evaluating the quality of the enrolled studies.
 Results: A total of 27 studies (totaling 5,105 patients and 5196 controls) were identified. The overall effect suggested ACE I/D was significantly associated with primary hypertension (OR: 95%CI=1.51[1.29-1.77], p=0.004). There was no association between AGT M235T with risk of essential hypertension.
 Conclusion: This meta-analysis found significant association between ACE I/D gene polymorphisms with primary hypertension susceptibility. However, the AGT M235T gene had no association with the risk of primary hypertension. The Adrenoreceptor-beta/Renin Angiotensin System (ADRB/RAS) A allele should be considered a risk factor for essential hypertension.

A study of the association between angiotensinogen (AGT) gene polymorphism (M235T) and preeclampsia in Thai pregnant women

AGT M235T gene polymorphism may cause increased blood pressure in preeclampsia in pregnancy; however, the evidence remains controversial. This study investigated the association between AGT M235T and preeclampsia in Thai pregnant women. A case-control study was conducted to compare the distributions of AGT M235T genotypes and alleles between 142 normotensive pregnancies as controls and 61 preeclampsia pregnancies as cases in a tertiary-care university hospital in Chiang Mai, Thailand. The results show that the distribution of AGT M235T genotypes (MM, MT and TT) of both groups were not significantly different (preeclampsia: 0.0, 16.4, 83.6%; control: 2.1, 22.5, 75.4%, respectively; p = .30). Additionally, there was no statistical difference in the distribution of AGT M235T alleles (M and T alleles) (preeclampsia: 8.2 and 91.8% versus control: 13.4 and 86.6%, respectively; p = .14). In this study, the distributions of AGT M235T were not different in both groups. Therefore, AGT M235T polymorphism may not play a significant role in preeclampsia pathophysiology in Thai population. Impact statement What is already known on this subject? Preeclampsia is one of the major complications during pregnancy; it significantly affects maternal and perinatal morbidity and mortality. Effort has been made to find markers and predictors that are associated with the pathophysiology of preeclampsia. AGT M235T gene polymorphism may cause increased blood pressure in preeclampsia pregnancy; however, evidences are still controversial. What do the results of this study add? We conducted a case-control study to compare the distributions of AGT M235T genotypes and alleles between 142 normotensive pregnancies as controls and 61 preeclampsia pregnancies as cases. The results show that preeclamptic women are more likely to deliver at an earlier gestational age and have a smaller baby in comparison with the normotensive group. In addition, women with preeclampsia had a higher chance of having an operative delivery and caesarean section. However, the distribution of AGT M235T polymorphism of preeclampsia women and the control group were not significantly different. What are the implications of these findings for clinical practice and/or further research? AGT M235T polymorphism may not play a significant role in preeclampsia pathophysiology in Thai population.

Angiotensinogen M235T polymorphism and susceptibility to hypertrophic cardiomyopathy in Asian population: A meta analysis.

Objective:To explore the relationship between the polymorphism of angiotensinogen gene (AGT) M235T and susceptibility to hypertrophic cardiomyopathy (HCM) in Asian population by meta-analysis.Methods:PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, and other databases were searched to collect the literature about AGT M235T polymorphism and HCM from the inception to March 1, 2020. The Newcastle-Ottawa Scale (NOS) checklist was uesd to perform independent literature review and study quality assessment. Data was analyzed by Stata 15.0 software.Results:The results showed that, except for the recessive genetic model (TT vs MT+MM: OR = 1.27, 95%CI: 1.05–1.53), in the other four genetic models, the M235T polymorphism had no significant correlation with the risk of HCM (T vs M: OR = 1.17, 95%CI: 0.88–1.57; TT+MT vs MM: OR = 1.13, 95%CI: 0.55–2.33; TT vs MM: OR = 1.25, 95%CI: 0.60–2.59; TM vs MM: OR = 0.95, 95%CI0.5–1.82). The results of subgroup analysis showed that, except for the heterozygous genetic model, in the other four genetic models, M235T polymorphism was significantly associated with sporadic hypertrophic cardiomyopathy (SHCM), but not with familial hypertrophic cardiomyopathy (FHCM) (p > 0.05).Conclusion:M235T polymorphism in Asians is associated with HCM, especially SHCM. Heterozygotes increase the risk of patients with SHCM.

Polymorphism of genes of renin-angiotensin-aldosterone system in the development of hypertension in workers exposed to physical factors

Introduction. The problem of reducing the risk of cardiovascular disease among the working population today remains the most urgent. One risk factor for arterial hypertension (AH) is exposure to high levels of noise and vibration in the workplace. Along with occupational risk factors, hereditary predisposition makes a significant contribution to the development of AH. In the pathogenesis of AH, a special role is played by genes that determine the synthesis of angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin receptor type 1 (AGTR1), etc.The aim of the study was to study the polymorphism of genes of the renin-angiotensin-aldosterone system in the development of hypertension in workers exposed to physical factors (noise and vibration) in the workplace.Materials and methods. A survey of 123 men working in «Kolomna plant» (KP), 84 of them-workers who were exposed to physical factors, and 39 people who are not in contact with harmful industrial factors. Th e presence/absence of GD, the age of its beginning, blood pressure, heart rate, the total experience of work on the KP in harmful conditions were assessed on outpatient cards. Molecular genetic studies of polymorphic genes of renin-angiotensin-aldosterone system (ALU Ins/Del of ACE gene, M235T of AGT gene, a1166c of AGTR1 gene) were carried out for all examined patients.Results. The results of correlation analysis showed the presence of a significant (р<0,05) relationship between AH and noise γ=0.42 p=0.0004, total vibration γ=0.57 p=0.002, heating microclimate γ=0.57 p=0.01. The correlation between the presence of polymorphic variant M235T AGT gene and GB γ=0.35 p=0.001, as well as levels of SAD γ=0.28 p=0.00054 and dad γ=0.29 p=0.00053 in the group of workers exposed to noise was revealed. A significantly higher prevalence of the SS genotype of the AGT gene was also found in the group of workers with AH compared to carriers of the TT variant χ2=6.18 p=0.013 and all carriers (SS+ST) of the C allele compared to carriers of the allele T χ2=6.0 p=0.014. An Association between increased SAD and the presence of the ACE gene allele D (Alu Ins/Del) and the AGTR1 gene allele C (A1166C) in individuals exposed to noise and vibration in the workplace was revealed.Conclusions. The obtained results indicate the multifactorial nature of hypertension, the importance of occupational factors in the formation of AH, primarily noise and vibration, and genetic factors: homozygous variant of the CC gene AGT (Met235Th r), the presence of the d allele of the ACE gene (Alu Ins/Del) and the C allele of the AGTR1 gene (A1166C).

Angiotensinogen M235T Gene Polymorphism is a Genetic Determinant of Cerebrovascular and Cardiopulmonary Morbidity in Adolescents with Sickle Cell Disease

BackgroundCerebrovascular stroke is a common critical complication of sickle cell disease (SCD). Angiotensinogen (AGT) M235T gene polymorphism is associated with risk of ischemic stroke and cardiovascular disease. AimWe investigated the potential association between angiotensinogen M235T gene polymorphism and susceptibility to cerebrovascular and cardiopulmonary complications in adolescents with SCD. MethodsForty-six patients with SCD in steady state were studied stressing on history of stroke, hydroxyurea/chelation therapy, hematological profile, and echocardiographic findings. Polymerase chain reaction-based restriction fragment length polymorphism analysis was used to detect AGT M235T gene polymorphism. Fifty sex- and age-matched healthy controls were enrolled for assessment of M235T gene polymorphism pattern. ResultsThe distribution of AGT M235T gene polymorphism was similar between SCD patients and healthy controls. The frequency of T allele of AGT M235T gene polymorphism (TT and MT genotypes) was significantly higher among patients with history of manifest stroke (P < .001). Patients with TT and MT genotypes had higher incidence of cardiopulmonary complications (P = .041) as well as higher percentage of HbS (P < .001) and lower hemoglobin level (P = .008) compared with those with MM genotype. Serum ferritin, liver iron concentration, and cardiac T2* were not related to T alleles or genotypes. Logistic regression analysis revealed that M235T genotype was a significant independent factor related to the occurrence of stroke among patients with SCD (Odds Ratio 14.05, 95% confidence interval 3.82-28.91; P = .001). ConclusionAGT M235T gene polymorphism may represent a genetic modifier to vascular morbidities in Egyptian patients with SCD.

27 RELATIONSHIP BETWEEN GENETIC POLYMORPHISM OF ANGIOTENSINOGEN M235T GENE AND ESSENTIAL HYPERTENSION AMONG ETHNICS IN SOUTHEAST SULAWESI

Background: The studies on genetic polymorphism of angiotensinogen M235T gene conducted in several countries showed that the emergence of allele 235T among Asians had increased the risk of hypertension compared to Caucasians. Nevertheless, relations between angiotensinogen gene polymorphism and essential hypertension risk on intra-populations of asian people between ethnics is still less consistent. Objective: This study aimed to examine the relationship in polymorphism of angiotensinogen M235T gene as a risk factor causing essential hypertension among ethnics in Southeast Sulawesi. Method: This research used cross sectional study design. Sixty-one genetic samples (peripheral venous blood from 53 hypertensive and 8 normotensive subjects) were processed through polymerase chain reaction and restriction fragment length polymerase. Results: Tolaki ethnic who had homozygous TT genotype were 27 samples (44.3% of total sample) and homozygous MT genotype were 6 samples (9.8%). Muna ethnic who had homozygous TT genotype were 22 samples (36.1%) and there were no heterozygous MT genotype. Buton ethnic who had homozygous TT genotype were 5 samples (8.2%) dan heterozygous MT genotype was found in 1 sample (1.6%). Overall, the numbers of homozygous TT genotype were 54 samples (88.5%), homozygous MT genotypes were 7 (11.5%) and no subject was homozygous MM genotype. Among the hypertensive group, 46 were TT genotype and 7 were MT genotype. In the normotensive group (all 8 samples), only TT genotype was found (chi-square 1.94, p-value 0.275). Conclusion: This study concluded that there was no relationship between polymorphism of Angiotensinogen M235T gene and essential hypertension among ethnics in Southeast Sulawesi.

Increased Plasma Angiotensinogen Level, BMI and Its Association with the Angiotensinogen Gene M235T Polymorphism and Essential Hypertension in Myanmar

Increased Plasma Angiotensinogen Level, BMI and Its Association with the Angiotensinogen Gene M235T Polymorphism and Essential Hypertension in Myanmar

Association of maternal angiotensinogen gene M235T polymorphism with preeclampsia in South India: A tertiary care hospital based case-control study

PurposeM235T polymorphism (rs699) in angiotensinogen (AGT) gene is associated with the risk of developing preeclampsia. This case-control study examines the profile of AGT M235T polymorphism in preeclamptic and normotensive pregnancies in a South Indian population. MethodsA total of 300 women comprising of 150 preeclamptic pregnancies and an equal number of normotensive pregnancies were enrolled in the study. AGT M235T polymorphism was determined by PCR-RFLP technique. Differences in the distribution of alleles and genotypes among cases and controls was evaluated for statistical significance by means of contingency table. ResultsThe presence of AGT 235 T allele was found to be associated with the increased risk of developing preeclampsia [P=0.003, odds ratio=1.69 (95% CI: 1.20–2.38)]. At the genotype level, the odds ratio for the risk of PE was 2.52 (95% CI: 1.25–5.07) and 1.67 (95% CI: 1.05–2.63) in the dominant and recessive models respectively. ConclusionsOur results support the conclusion that AGT M235T polymorphism is associated with increased risk of developing preeclampsia in the South Indian population. This is the first study to report a positive association between AGT M235T polymorphism and preeclampsia in the Indian population.

Association study between some renin-angiotensin system gene variants and essential hypertension in a sample of Algerian population: case control study.

Essential hypertension is an important risk factor for the development of cardiovascular disease. We aim in this study to analyse the relationship between AGT M235T gene variant and ACE I/D gene variant with essential hypertension in a sample of the Algerian population of the Oran city. A case-control study has been performed in 145 subjects including; 75 hypertensives and 70 controls from Algerian population of Oran city. Polymerase chain reaction (PCR) combined with restrictive fragment length polymorphism (RFLP) was used to detect the M235T variant of angiotensinogen (AGT) gene and a nested PCR to determine ACE I/D gene variant. The genotypic and allelic distribution of the M235Tvariant of the AGT gene did not differ in hypertensives and normotensives group (X(2) =7.81, P<0.05; X(2) =4.67, respectively) thus there was no association between the T allele and hypertension (OR=1.64; 95%CI [1.01-2.69]). The genotypic and allelic frequencies of the ACE I/D variant did differ significantly between hypertensives and controls (X(2)=13.98, P<0.05; X(2) =12.66, P<0.05, respectively) where a significant association between the D allele of the ACE I/D gene and essential hypertension has been observed (OR=0.46; 95%CI [0.27-0.75]). We reported a high prevalence of the D and T allele in hypertensives female. This study shows that the M235T variant of the AGT gene is not associated with essential hypertension while a significant association has been reported with the D allele in this sample of Algerian population of the Oran city.

Angiotensinogen Gene M235T and T174M Polymorphisms in Patients with Morbid Obesity and Type 2 Diabetes Mellitus

Background: Angiotensinogen and its cleaved form - angiotensin II are important regulators of adipose tissue metabolism and they may affect adipogenesis. Aim: We studied the correlation between M235T and T174M polymorphisms of angiotensinogen (AGT) gene and morbid obesity and their association with Type 2 Diabetes Mellitus (T2DM). We also investigated the role of haplotypes formed by these polymorphisms in the risk for extreme obesity and obesity- associated T2DM. Material and methods: The study included 335 morbidly obese patients (study groups) and 230 subjects without obesity (control group). The molecular analysis was performed using Polymerase Chain Reaction (PCR) and PCR-restriction fragment length polymorphism technique. Results: Distribution of the genotype for AGT M235T polymorphism differed significantly between the controls and all extremely obese patients (p 0.1). AGT gene polymorphic variants did not display any difference in clinical or metabolic parameters according to each genotype for either the control or the morbidly obese group. In univariate logistic regression analysis, the carriers for T235T and T174M (Hap2Hap3) had lower risk for extreme obesity (p<0.05). Homozygosity for both T235T and T174T (Hap2Hap2) was associated with decreased risk for extreme obesity and concomitant T2DM (p<0.05). Conclusion: M235T but not T174M polymorphism of angiotensinogen (AGT) gene, may be linked with extreme obesity and T2DM in the investigated group of patients. On the basis of our results, we suggest that the risk of extreme obesity, irrespective of T2DM, was lower in Hap2Hap3 haplotype pair carriers. The Hap2Hap2 haplotype pair may be a significant protective factor for morbid obesity with T2DM and T2DM development in extreme obesity status (p<0.05).

RETRACTED: Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy.

The following article has been included in a multiple retraction: Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System ( JRAAS) 1470320314563424, first published 18 December 2014. DOI: 10.1177/1470320314563424 . This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the JRAAS (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer-review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online-first articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy JRAAS 1470320314563426, first published 18 December 2014. DOI: 10.1177/1470320314563426 . Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy JRAAS 1470320314563424, first published 18 December 2014. DOI: 10.1177/1470320314563424 . Weiqiang Zhong, Zongpei Jiang and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population JRAAS1470320314566019, first published 26 January 2015. DOI: 10.1177/1470320314566019 . Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population JRAAS 1470320314563425, first published 1 February 2015. DOI: 10.1177/1470320314563425 . Chun-Hua Yang and Tian-Biao Zhou Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy JRAAS 1470320314566221, first published 1 February 2015. DOI: 10.1177/1470320314566221 . Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression JRAAS 1470320314568521, first published 3 February 2015. DOI: 10.1177/1470320314568521 . Articles published in an issue Guohui Liu, Tian-Biao Zhou, Zongpei Jiang and Dongwen Zheng Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population JRAAS March 2015; 16: 165-171, first published 14 November 2014. DOI: 10.1177/1470320314557849 . Weiqiang Zhong, Zhongliang Huang, Yong Wu, Zongpei Jiang and Tian-Biao Zhou Association of aldosterone synthase ( CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathy JRAAS September 2015; 16: 660-665, first published 20 August 2014. DOI: 10.1177/1470320314524011 .

RETRACTED: Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy.

This article has been included in a multiple retraction: Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 Chun-Hua Yang and Tian-Biao Zhou Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314566221, first published on February 1, 2015 doi: 10.1177/1470320314566221 Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 Articles published in an issue Guohui Liu, Tian-Biao Zhou, Zongpei Jiang, and Dongwen Zheng Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population Journal of Renin-Angiotensin-Aldosterone System March 2015 16: 165-171, first published on November 14, 2014 doi: 10.1177/1470320314557849 Weiqiang Zhong, Zhongliang Huang, Yong Wu, Zongpei Jiang, and Tian-Biao Zhou Association of aldosterone synthase (CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathy Journal of Renin-Angiotensin-Aldosterone System September 2015 16: 660-665, first published on August 20, 2014 doi: 10.1177/1470320314524011.

The angiotensinogen gene polymorphism is associated with heart failure among Asians

The angiotensinogen (AGT) gene M235T polymorphism has been suggested to be linked to risk of heart failure (HF). However, association studies on the M235T polymorphism and HF risk have shown conflicting results. PubMed and China Biology Medicine (CBM) databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 1,281 HF cases and 1,376 controls were included in the analysis. The pooled data showed that there was no significant associations between the AGT M235T polymorphism and HF risk for TT vs. MM (OR = 1.17, 95%CI = 0.62–2.19, P = 0.635), MT vs. MM (OR = 0.97, 95%CI = 0.77–1.22, P = 0.776), MT/TT vs. MM (OR = 1.07, 95%CI = 0.67–1.69, P = 0.781), and TT vs. MM/MT (OR = 1.23, 95%CI = 0.86–1.76, P = 0.259). In contrast, in the HF subgroup analysis by ethnicity, the AGT M235T polymorphism had a decreased risk of HF among Asians (MT vs. MM, OR = 0.39, 95%CI = 0.17–0.92, P = 0.032). Our results suggest that the AGT M235T polymorphism is a low-penetrant risk factor for the development of HF among Asians.

Survival and Predictive Factors of Lethality in Hemodyalisis: D/I Polymorphism of The Angiotensin I-Converting Enzyme and of the Angiotensinogen M235T Genes

BackgroundEnd-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes.ObjectiveTo assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis.MethodsOur study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value ≤ 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study.ResultsThe mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor.ConclusionsThe survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene.

The influence of renin-angiotensin system genotypes on the antiproteinuric response to high doses of olmesartan in non-diabetic proteinuric nephropathies.

To assess the antiproteinuric response to multifactorial treatment based on high doses of angiotensin II receptor antagonists (ARBs) (olmesartan) in patients with non-diabetic proteinuric nephropathies, according to three renin-angiotensin system (RAS) polymorphisms: insertion/deletion of the angiotensin converting enzyme (ACE) gene, the angiotensinogen gene M235T and the angiotensin II type 1 receptor (AT1R) A1166C. We studied 53 patients with non-diabetic proteinuric nephropathy with a mean progression time of 84.4±15 months. 41 were males (77.4%); mean age 49.7±3 years, body mass index 30±6kg/m2. All received olmesartan (40mg/12h) associated with a mean of 2.4±1.6 antihypertensive drugs for a median period of 13 months (interquartile range 7-25 months). Systolic blood pressure (BP) decreased from 145±14mmHg to 128±14mmHg (P<.001) and diastolic BP from 85±11mmHg to 79±7mmHg (P<.01). Pulse pressure decreased from 53.5±14mmHg to 48±12mmHg (P<.05). Proteinuria decreased from 2.74±1.6g/24h to 0.9±1g/24h (P<.001), representing a mean decrease of 67.1%. According to RAS polymorphisms, antiproteinuric response was: angiotensinogen gene polymorphism: genotype TT: 76.8%; genotype MM: 67.3%; genotype MT: 65.8%, significantly higher (P<.05) for genotype TT compared to genotypes MM and MT. Polymorphism of the ACE gene: genotype DD: 71.4%; genotype ID: 60.6%, genotype II: 34.8%, significantly higher (P<.05) for genotype DD compared to genotypes ID and II, and also (P<.05) for genotype ID compared to II. AT1R gene polymorphism: genotype AC: 85.2%; genotype CC: 73.7%; genotype AA: 62.7%; significantly higher for genotype AC (P<.05) compared to genotypes AA and CC. The differences between initial and final proteinuria for the follow-up period were significant (P<.01) for genotypic associations DD/AA, DD/MT, DD/MM, DD/TT and DD/AC, although the association with the highest antiproteinuric effect was DD/AC (89.9%, P<.05%). Administering high doses of olmesartan in patients with non-diabetic proteinuric nephropathy results in significant reductions in proteinuria. This decrease was independent of blood pressure control and other confounding factors. RAS polymorphisms may modulate the antiproteinuric response to treatment with ARBs.

Polymorphism of angiotensinogen gene M235T in myocardial infarction and brain infarction: a meta-analysis

The angiotensinogen (AGT) gene M235T polymorphism has been reported to be associated with myocardial infarction (MI) and brain infarction (BI), but the results remain inconclusive. This meta-analysis was designed to clarify these controversies. Electronic databases were systematically searched before February 2013. A total of 38 studies with 17304 subjects met our inclusion criteria. In East Asian group, significant association was found between AGT M235T polymorphism and risk of MI (for dominant model: OR=1.79; 95% CI=1.04–3.06; for recessive model OR=2.01; 95% CI=1.21–3.36; for additive model OR=1.79; 95% CI=1.14–2.86) as well as BI (for dominant model: OR=1.66; 95% CI=1.22–2.27; for recessive model OR=1.78, 95% CI=1.29–2.46; for additive model: OR=1.64, 95% CI=1.34–2.00), while the M235T polymorphism did not impact the risk of MI in total population and other ethnicity. In the subgroup analyses by gender and age, there was lack of evidence for the association. This meta-analysis suggested an association between the M235T polymorphism and MI as well as BI in East Asian population. Further studies with larger numbers of worldwide participants are needed to understand the genetic basis of MI and BI.

INFLUENCE OF THE POLYMORPHISM OF THE RENIN-ANGIOTENSIN SYSTEM GENES ON THE CARDIAC ARRHYTHMIAS IN CHILDREN WITH HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCMP) is a genetically determined myocardial disease, characterized by massive hypertrophy of the myocardium of the left and/or (rarely) the right ventricle, often associated with obstruction of the left ventricular outflow tract and diastolic dysfunction. The course of disease can be complicated by development of various cardiac arrhythmias. It was reported that severity of HCMP course depends at certain degree on polymorphism of candidate genes, including genes of the renin angiotensin system (RAS). Influence of RAS genes polymorphism on the frequency and character of cardiac arrhythmias in childhood is almost not studied. Aim : to determine the influence of RAS genes polymorphism on the prevalence and structure of cardiac arrhythmias in children with HCMP. Patients and methods : analysis of influence of RAS genes polymorphism on the prevalence and structure of cardiac arrhythmias was performed in 32 children with HCMP. All the patients were carried out ECG, cardiac ultrasound and ECG Holter monitoring. Polymorphism of the RAS genes (renin gene (REN) G83A, angiotensinogen gene (AGT) M235T, angiotensin-converting enzyme gene (ACE) I/D, angiotensin II receptor type 1 gene (AGTR1) A1166C). Results : in patients with HCMP was established a higher frequency of TT-genotype and T-alleles of angiotensinogen gene than in comparison group. In homozygous patients with T-allele of angiotensinogen gene ventricular arrhythmia was found reliably more often than in patients with MT- and MM-genotypes, which suggested that M235T polymorphism of angiotensinogen gene influenced on intensity of ventricular arrhythmias in children with HCMP. Conclusions : in children with HCMP and cardiac arrhythmias analysis of M235T polymorphism of angiotensinogen gene can be used as an additional criterion for revealing of patients with high risk of arrhythmic complications and for development of preventative measures.

The angiotensinogen gene M235T polymorphism and acute myocardial infarction risk: a meta-analysis of 22 studies

Angiotensinogen, one of the most important proteins in the renin-angiotensin system, plays a key role in the progress of coronary heart disease and myocardial infarction (MI). Many studies have investigated the association between angiotensinogen gene M235T polymorphism and MI risk, but the results were inconsistent. We performed a meta-analysis of 22 studies on M235T polymorphism and MI risk published before November 2012. This meta-analysis included a total of 4,606 MI cases and 4,918 controls. Overall, the per-allele odds ratio (OR) of the 235T variant for total MI risk was 1.04 (95 % CI 0.92-1.17). When a recessive model was evaluated, the OR was 1.06 (95 % CI 0.96-1.17) and under a dominant model, the OR was 0.96 (95 % CI 0.82-1.11). Under pairwise comparisons, non-significant associations were found between M235T polymorphism and MI risk (MT vs. MM, OR, 0.96, 95 % CI 0.87-1.06; TT vs. MM, OR, 1.03, 95 % CI 0.83-1.28). Subgroup analyses in the different ethnic groups and different control sources were performed and no significant association was found also. Based on the available evidence, no association between M235T polymorphism and MI risk was observed, even in the sub-analysis concerning different races and control sources. The direction of further research should focus not only on the simple relationship of M235T polymorphism and MI risk, but also on gene-gene and gene-environment interaction.