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Fulltext Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen

Joyce-Tan SM, Zain SM, Abdul Sattar MZ, Abdullah NA

J Diabetes Res, 2016;2016:2161376.
PMID: 26682227 DOI: 10.1155/2016/2161376

Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls for AGT variants (P = 0.05) but not for ACE and AGTR1. Haplotype TCG of the AGT was associated with increased risk of T2DM (OR 1.92, 95% CI 1.15-3.20, permuted P = 0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of the AGT variants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.

Matched MeSH terms: Angiotensinogen/genetics*
Fulltext Angiotensinogen M235T gene variants and its association with essential hypertension and plasma renin activity in Malaysian subjects: a case control study

Say YH, Ling KH, Duraisamy G, Isaac S, Rosli R

BMC Cardiovasc Disord, 2005;5(1):7.
PMID: 15811183

Essential hypertension is a major public health concern worldwide where its prevalence accounts for various cerebrovascular diseases. A common molecular variant of angiotensinogen (AGT), the precursor of potent vasoactive hormone angiotensin II, has been incriminated as a marker for genetic predisposition to essential hypertension in some ethnics. This case-control study was designed not only to determine the association of the AGT M235T gene variants with essential hypertension, but also its relationship to Plasma Renin Activity (PRA) in subjects attending the Health Clinic, Kuala Lumpur, Malaysia.

Matched MeSH terms: Angiotensinogen/genetics*
Renin-Angiotensin-Aldosterone System Gene Polymorphisms and Type 2 Diabetic Nephropathy in Asian Populations: An Updated Meta-analysis

Ahmad N, Jamal R, Shah SA, Gafor AHA, Murad NAA

Curr Diabetes Rev, 2019;15(4):263-276.
PMID: 29984662 DOI: 10.2174/1573399814666180709100411

BACKGROUND: 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.
OBJECTIVE: This meta-analysis aimed to assess the updated pooled effects of these polymorphisms with DN among Asian populations with type 2 diabetes mellitus.
METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.

Matched MeSH terms: Angiotensinogen/genetics
Candidate gene polymorphisms and their association with hypertension in Malays

Ghazali DM, Rehman A, Abdul Rahman AR

Clin Chim Acta, 2008 Feb;388(1-2):46-50.
PMID: 17977523 DOI: 10.1016/j.cca.2007.10.002

BACKGROUND: Knowledge of candidate gene polymorphisms in a population is useful for a variety of gene-disease association studies, particularly for some complex traits. A single nucleotide variant of the angiotensinogene gene (AGT M235T) and endothelial nitric oxide synthase gene (eNOS G894T) have been associated with hypertension.
METHOD: A cross-sectional study consisting of 200 hypertensives and 198 age- and sex-matched controls was conducted. Subjects involved in this study were pure Malay for 3 generations. The AGT M235T and eNOS G894T polymorphisms were determined by PCR-RFLP method.
RESULTS: The distribution of M235T genotype in the population was 3.5% for MM, 30.4% for MT and 66.1% for TT. No significant difference was observed in genotype (chi(2)=1.30, p=0.52) and allele (chi(2)=0.87, p=0.35) frequencies among the 2 study group. In contrast, the distribution of genotypes for G894T was 74.1% for GG, 24.6% for GT and 1.3% for TT, respectively. Similarly, no significant difference was observed in genotype (chi(2)=0.94, p=0.33) and allele (chi(2)=0.60, p=0.44) frequencies between both study groups.
CONCLUSION: The AGT M235T and eNOS G894T polymorphisms are unlikely to play an important role in the pathogenesis of hypertension in Malays.
Study site: Outpatient clinic, Hospital Universiti Sains Malaysia (HUSM); government clinics, Kelantan, Malaysia.

Matched MeSH terms: Angiotensinogen/genetics
Fulltext Genetic Predictors of Salt Sensitivity of Blood Pressure: The Additive Impact of 2 Hits in the Same Biological Pathway

Haas AV, En Yee L, Yuan YE, Wong YH, Hopkins PN, Jeunemaitre X, et al.

Hypertension, 2021 Dec;78(6):1809-1817.
PMID: 34757767 DOI: 10.1161/HYPERTENSIONAHA.121.18033

[Figure: see text].

Matched MeSH terms: Angiotensinogen/genetics*
Fulltext Analysis of renin-angiotensin aldosterone system gene polymorphisms in Malaysian essential hypertensive and type 2 diabetic subjects

Ramachandran V, Ismail P, Stanslas J, Shamsudin N

Cardiovasc Diabetol, 2009;8:11.
PMID: 19243623 DOI: 10.1186/1475-2840-8-11

The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects.

Matched MeSH terms: Angiotensinogen/genetics*
Fulltext Gene Polymorphisms of the Renin-Angiotensin-Aldosterone System as Risk Factors for the Development of In-Stent Restenosis in Patients with Stable Coronary Artery Disease

Azova M, Timizheva K, Ait Aissa A, Blagonravov M, Gigani O, Aghajanyan A, et al.

Biomolecules, 2021 05 20;11(5).
PMID: 34065198 DOI: 10.3390/biom11050763

This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.

Matched MeSH terms: Angiotensinogen/genetics