Angiotensinogen M235T Polymorphism Research Articles

Impact of the gene polymorphisms in the renin-angiotensin system on cardiomyopathy risk: A meta-analysis.

Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy remains unclear. In this study, we conducted a systematic review and meta-analysis to summarize the findings regarding the impact of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin II Type 1 receptor (AGTR1) A1166C gene polymorphisms in patients with cardiomyopathy. We performed a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, covering articles published from the time of database creation to April 17, 2023. Studies on the assessment of genetic polymorphisms in genes related to the renin-angiotensin system in relation to cardiomyopathy were included. The primary outcome was cardiomyopathy. Risk of bias was assessed using the Newcastle-Ottawa Scale scale. The meta-analysis includes 19 studies with 4,052 cases and 5,592 controls. The ACE I/D polymorphisms were found to be associated with cardiomyopathy (allelic model D vs I: OR = 1.29, 95CI% = 1.08-1.52; dominant model DD+ID vs II: OR = 1.43, 95CI% = 1.01-2.02; recessive model DD vs ID+II: OR = 0.79, 95CI% = 0.64-0.98). AGT M235T polymorphism and cardiomyopathy were not significantly correlated (allelic model T vs M: OR = 1.26, 95CI% = 0.96-1.66; dominant model TT+MT vs MM: OR = 1.30, 95CI% = 0.98-1.73; recessive model TT vs MT+MM: OR = 0.63, 95CI% = 0.37-1.07). AGTR1 polymorphism and cardiomyopathy were not significantly associated under allelic model A vs C (OR = 0.69, 95CI% = 0.46-1.03) and recessive model AA vs CA+CC (OR = 0.89, 95CI% = 0.34-2.30), but under the dominant model AA+CA vs CC (OR = 0.51, 95CI% = 0.38-0.68). The current meta-analysis reveals that polymorphisms in ACE I/D may be a genetic risk factor for cardiomyopathy. There is an association between AGTR1 gene polymorphisms and risk of cardiomyopathy under the specific model.

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.

Handgrip Strength is more associated with blood glucose than ACE and AGT polymorphisms in hemodialysus patients

Background: Patients with chronic kidney disease (CKD) often present with comorbidities like hypertension and diabetes. These conditions are often associated with loss of strength, which is a strong predictor of mortality. In this sense, it is reasonable to investigate genetic and physiological markers that could be related to strength and identify variables associated with this phenomenon. Objective: This study aimed to investigate the influence of angiotensin-1 converting enzyme (ACE) and angiotensinogen (AGT) M235T polymorphisms, and blood glucose on handgrip strength (HGS) for CKD patients with and without diabetes mellitus (DM). Methods: Male patients (n = 84) participated in this cross-sectional study. Patients were grouped based on the diagnosis of DM or not. We evaluated HGS using a dynamometer and ACE and AGT polymorphism by polymerase chain reaction. Results: There were differences in HGS between groups. Follow up analyses indicated a difference in the distribution of ACE polymorphism alleles was associated with the reduction in HGS in the DM group. The same response was present for AGT. A negative correlation existed between blood glucose levels and HGS (r = -0.334 with p < 0.05). Discussion: The present data suggests that there is a relationship between physical capacity and poor glycemic control. Conclusion: Our study demonstrated that blood glucose levels are associated with HGS in patients with CKD independent of ACE I/D and AGT M235T polymorphisms. Presence of DM may influence functional strength retention.

AGT M235T Polymorphism and Arterial Hypertension in Patients with Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) represents an important public health challenge. It is a major cause of chronic morbidity and mortality throughout the world. Arterial hypertension (AH) is considered one of the principal COPD-associated comorbidities. Objective: The study was aimed to assess the role of angiotensinogen (AGT) gene polymorphism in occurrence of AH in patients with COPD. Methods: The study was conducted among 96 patients of them, Group 1 (25 individuals with COPD), Group 2 (23 individuals with AH), Group 3 (28 individuals with COPD and AH). The control group consisted of the 20 healthy subjects. I/D genotypes of AGT were determined by polymerase chain reaction amplification. Plasma AGT activity was determined photometrically by a commercially available kit. Results: The results of the study have not demonstrated any significant impact of alleles of AGT genes on occurrence of such disease as COPD, AH and combinations thereof. However, analysis of odds ratio has demonstrated the presence of a trend towards a protective role of the M allele of the AGT gene concerning occurrence of COPD, AH and their combinations (OR=0.90, OR=0.71 and OR=0.56, respectively). At the same time, the presence of the T allele of the AGT gene may increase the risk for occurrence of the above mentioned disease (OR=1.11, OR=1.4 and OR=1.79, respectively). Conclusion: The study suggests that the presence of Т allele of the AGT gene at position 235 of the peptide chain both in homozygous and heterozygous state may increase the risk for AH in patients with COPD. Bangladesh Med Res Counc Bull 2020; 46(3): 176-183

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.

Association between arterial hypertension and chronic obstructive pulmonary disease: role of AGT gene polymorphism

Abstract Background Chronic obstructive pulmonary disease (COPD) continues to cause a heavy health and economic burden in the Europe and around the world. Arterial hypertension (AH) is considered as one of the principal COPD-associated comorbidi-ties. However, no data for association between gene polymorphism and AH in patients with COPD in Ukraine have ever been internationally published. We assessed the genotype and allele frequencies of angiotensinogen (AGT) M235T polymorphisms in patients with COPD and comorbid AH. Methods The study group consisted of 96 patients: Group 1 (25 individuals with COPD), Group 2 (23 individuals with AH) and Group 3 (28 individuals with COPD and AH). The control group consisted of 20 healthy subjects. M/T genotypes of AGT were determined by polymerase chain reaction amplification. Results The results of the study have not demonstrated any significant impact of alleles of AGT genes on the occurrence of diseases such as COPD, AH and combinations thereof. However, analysis of odds ratio has demonstrated the presence of a trend towards a protective role of the M allele of the AGT gene concerning occurrence of COPD, AH and their combinations. At the same time, the presence of the T allele of the AGT gene may increase the risk for occurrence of the above-mentioned diseases. Conclusions The study that we have conducted suggests that the presence of T allele of the AGT gene at position 235 of the peptide chain both in homozygous and heterozygous states may increase the risk for AH in patients with COPD.

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.

M235T polymorphism in the angiotensinogen gene and cardiovascular disease: An updated meta-analysis of 39 case-control comparisons.

Objective:M235T polymorphism of the angiotensinogen (AGT) gene has been linked with cardiovascular disease (CVD). The aim of this meta-analysis was to investigate whether combined evidence supports this association.Methods:A systematic search was conducted for studies published up to October 2018 that evaluate the association between AGT M235T polymorphism and risk of CVD. Case–control studies were identified, and the association between AGT M235T polymorphism and CVD risk was assessed using genetic models.Results:Thirty-nine comparisons from 38 studies were collected, and a meta-analysis and subgroup analysis was performed based on ethnicity. In the overall population (9225 cases and 8406 controls), the occurrence of CVD was found to be associated with AGT M235T polymorphism in both allelic [T vs. M: odds ratio (OR)=1.16] and recessive (TT vs. MT+MM: OR=1.14) models. In subgroup analyses, a significant association was identified between AGT M235T polymorphism and CVD risk in East Asian subgroups in allelic (T vs. M: OR=1.46), homozygous (TT vs. MM: OR=1.78), dominant (MT+TT vs. MM: OR=1.47), and recessive (TT vs. MT+ MM: OR=1.68) models, but there was no significant association in Caucasian populations.Conclusion:Among East Asians, the AGT variant M235T is associated with CVD risk. However, current evidence suggests that there is no such association in the Caucasian population.

Renin-Angiotensin-Aldosterone System Gene Polymorphisms and Type 2 Diabetic Nephropathy in Asian Populations: An Updated Meta-analysis.

The association of polymorphisms in the renin-angiotensin-aldosterone system candidate genes, namely Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D), Angiotensinogen (AGT) M235T and Angiotensin II Receptor Type 1 (AGTR1) A1166C with Diabetic Nephropathy (DN) has been studied for decades. This meta-analysis aimed to assess the updated pooled effects of these polymorphisms with DN among Asian populations with type 2 diabetes mellitus. The PubMed electronic database was searched without duration filter until August 2017 and the reference list of eligible studies was screened. The association of each polymorphism with DN was examined using odds ratio and its 95% confidence interval based on dominant, recessive and allele models. Subgroup analyses were conducted based on region, DN definition and DM duration. In the main analysis, the ACE I/D (all models) and AGTR1 A1166C (dominant model) showed a significant association with DN. The main analysis of the AGT M235T polymorphism did not yield significant findings. There were significant subgroup differences and indication of significantly higher odds for DN in terms of DM duration (≥10 years) for ACE I/D (all models), AGT M235T (recessive and allele models) and AGTR1 A1166C (recessive model). Significant subgroup differences were also observed for DN definition (advanced DN group) and region (South Asia) for AGTR1 A1166C (recessive model). In the Asian populations, ACE I/D and AGTR1 A1166C may contribute to DN susceptibility in patients with T2DM by different genetic models. However, the role of AGT M235T needs to be further evaluated.

Associations between angiotensinogen M235T polymorphisms and the risk of diabetic nephropathy: A meta-analysis

AimsThe aim of the present study was to clarify the potential relationship of angiotensinogen (AGT) M235T polymorphism and diabetic nephropathy (DN) risk. MethodsComprehensive electronic search in Pubmed, Web of Science, EBSCO, Embase, the Cochrane Library and China National Knowledge Infrastructure (CNKI) to find original articles about the association between AGT M235T polymorphism and DN risk published before 27 September 2017. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Heterogeneity across studies was assessed using I2 statistics. Random-effects model or Fixed-effects model was used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger's regression test. Analyses were performed by using Stata 15.0. ResultsOverall, 20 eligible studies involving a total of 3822 cases and 3911 controls were included in our meta-analysis. The results showed that AGT M235T polymorphism significantly increased DN risk in recessive model (T/T versus M/T + M/M: OR = 1.35, 95%CI (1.07–1.69), I2 = 63.8%, Z = 2.56, P = 0.010), homozygote model (T/T versus M/M: OR = 1.46, 95%CI (1.11–1.92), I2 = 62.4%, Z = 2.69, P = 0.007) and allele model (T versus M: OR = 1.17, 95%CI (1.01–1.35), I2 = 72.5%, Z = 2.14, P = 0.032); Subgroup analysis by ethnicity showed that AGT M235T polymorphism significantly increased DN risk in recessive model (T/T versus M/T + M/M: OR = 1.39, 95%CI (1.06–1.81), I2 = 66.6%, Z = 2.42, P = 0.016), homozygote model (T/T versus M/M: OR = 1.47, 95%CI (1.08–2.01), I2 = 67.7%, Z = 2.47, P = 0.013) and allele model (T versus M: OR = 1.18, 95%CI (1.02–1.37), I2 = 69.4%, Z = 2.26, P = 0.024) in Caucasian DM population; Subgroup analysis by clinical subtype of DM also showed that AGT M235T polymorphism significantly increased DN risk in recessive model (T/T versus M/T + M/M: OR = 1.28, 95%CI (1.05–1.57), I2 = 21.3%, Z = 2.40, P = 0.016), homozygote model (T/T versus M/M: OR = 1.41, 95%CI (1.04–1.92), I2 = 30.2%, Z = 2.23, P = 0.026) and allele model (T versus M: OR = 1.14, 95%CI (1.03–1.28), I2 = 35.5%, Z = 2.44, P = 0.015) in type 1 diabetes patients. ConclusionOur study showed that AGT M235T homozygous mutation significantly increase DN risk in Caucasian DM population and type 1 diabetes patients.

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.

PP.30.16] EFFECTS OF THE ACE I/D GENE POLYMORPHISM ON ESRD PATIENTS SURVIVAL

Objective: It has been shown that genetic factors may influence the rate of death in ESRD patients. Genetic polymorphisms of the renin angiotensin system (RAS) have been associated with the development of cardiovascular disease and increased mortality. Design and method: Sixty patients with ESRD in hemodialysis with a mean age of 55 years were included in the study. The study population was genotyped for ACE insertion/deletion (I/D) polymorphism, angiotensinogen (AGT) M235T polymorphism and angiotensin II type receptor (AT1) A1166C polymorphism. Results: During a period of 79 months 45 patients died. Cumulative survival was significantly lower in individuals carrying the DD genotype compared with ID/II genotypes (p < 0.029). Estimated mean survival was 37 ± 5 months for patients with DD genotype and 52 ± 3.3 for patients with the DI/II genotypes. The comparison of conventional biochemical measures failed to identify differences that could be responsible for the increased mortality observed in patients with the DD genotype. Furthermore, in the study population there was no association between death and M235T or A1166C polymorphisms. Conclusions: These findings suggest that in hemodialysis patients homozygotes for the D allele of the ACE gene are at increased risk for total mortality.

The Association of Angiotensinogen (AGT M235T) Gene Polymorphism and Essential Hypertension in Thai Post-Menopausal Women

Objectives: This study aims to determine the relationship between angiotensinogen (AGT) M235T polymorphism and hypertension among post-menopausal Thai women. Materials and Methods: Case-control study was conducted. The study group was those who had hypertension or previously diagnosed and, the control were those who had no hypertension. Blood samples were taken for AGT M235T allelic characterization using allele specific oligonucleotides (ASO) PCR. Results: Of 255 post-menopausal women, 128 had hypertension, regarded as “hypertension group”, the other 127 without hypertension, regarded as “control group”. The presence of AGT M235T polymorphism was 76.5% for homozygous mutation (73.4% for hypertension group and 79.5% for control group), 21.2% for heterozygous mutation (25.0% for hypertension group and 17.3% for control group, respectively) and 2.4% for homozygous wild-type (1.6% for hypertension group and 3.2% for control group, respectively). Distribution of MM, MT and TT genotypes was not significantly different between both group (p=0.251). Conclusions: Interestingly, overall TT genotype was much higher than that of TM and MM in post-menopausal Thai women. AGT M235T polymorphism was not significantly associated with hypertension, though TT genotype tended to give a small risk. They may not serve as a good genetic marker for essential hypertension among Thai population.

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.

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.

Impact of common functional polymorphisms in renin angiotensin system genes on the risk of renal parenchymal scarring following childhood urinary tract infection

Pathogenesis of renal parenchymal scarring (RPS) after acute pyelonephritis (APN) is unclear. The risk of RPS varies markedly among individuals, suggesting a genetic role. To investigate a possible role of common polymorphisms in renin angiotensin system genes in APN-associated RPS in children. This study included 104 APN children and 300 controls. APN was diagnosed by urine culture and typical findings on 99Tc-DMSA scans. Voiding cystourethrogram tested the presence of vesicoureteral reflux (VUR). Follow-up DMSA scans were performed 4-6 months later to identify new RPS. Angiotensin converting enzyme gene I/D, angiotensin II receptor type-1 A1166C and angiotensinogen M235T polymorphisms were genotyped. New RPS developed in 44.2% (46/104) of children with APN. VUR was diagnosed in 35.6% (37/104) of APN cases. RPS developed in 73% of cases of VUR. The D allele of ACE gene I/D polymorphism was significantly more common in APN cases with RPS (73.91%) than non-RPS (58.6%) and controls (54.5%) (p = 0.021, p = 0.002, respectively). The AGTR-1 A1166C A allele was significantly more common in VUR than the non-reflux children (91.9% versus 76.1%; p = 0.005). VUR, in contrast to the D allele (OR 6.1, 95% CI 0.878-19.7; p = 0.05), was an independent risk factor for RPS. ACE gene D allele is associated with a twofold increase in RPS risk, which could be a result of a functional effect to increase tissue levels and activity of ACE during APN. However, D allele failed to qualify as an independent risk and its RPS association could be dependent on other co-factors, such as TGFβ1 activation, or the D-allele might link with recently discovered functional polymorphisms at the 5' end of the ACE gene. Although VUR is an independent risk for RPS, it is not clear whether this is due to exposure of the kidneys to infected urine, or VUR-associated dysplasia. In contrast with published literature, we noted higher rates of RPS and high-grade VUR, suggesting a more aggressive VUR course or local unawareness of APN. Our study has its limitations; the small number of VUR children, and the clinical and ethical difficulties of testing VCUG and DMSA in controls. ACE gene D allele is associated with, but cannot independently predict, RPS in children. VUR is an independent risk for post-pyelonephritic scarring. AGTR-1 1166A/C polymorphism is associated with occurrence, but not progression, of VUR.

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.

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).

A polymorphism inAGTandAGTR1gene is associated with lead-related high blood pressure

We investigated the association of polymorphisms in two renin-angiotensin system-related genes, expressed as angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1), with blood lead levels and lead-related blood pressure in lead-exposed male workers in Korea. A cross-sectional study involving 808 lead-exposed male workers in Korea was conducted using a restriction fragment length polymorphism-based strategy to differentiate the various genotypes of polymorphisms in the AGT and AGTR1 genes. The association of clinical characteristics with genotypes as modifiers was estimated after adjustment for age, smoking status, drinking status, body mass index and job duration of each subject. Genotype and allele frequencies of the M235T polymorphism in AGT were associated with lead-related high blood pressure status. Moreover, blood lead levels were associated with allele frequencies of the AGT M235T polymorphism. These results suggested that the M/M genotype and M allele of AGT are risk factors for lead-related high blood pressure.