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  1. 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: Renin-Angiotensin System/genetics*
  2. 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: Renin-Angiotensin System/genetics*
  3. Draman CR, Kong NC, Gafor AH, Rahman AF, Zainuddin S, Mustaffa WM, et al.
    Singapore Med J, 2008 Nov;49(11):924-9.
    PMID: 19037561
    Angiotensin-converting enzyme (ACE) gene polymorphism, especially the deletion/deletion (DD) genotype, is associated with the disease progression of immunoglobulin A (IgA) nephropathy patients in various studies from both Asia Pacific and European populations. However, recent studies within the same populations were unable to reproduce the same results. Hence, we had studied the distribution of the DD genotype, the association between ACE gene polymorphism and the disease progression, and the factors (other than ACE gene polymorphism) which were involved in the disease progression of our local patients.
    Matched MeSH terms: Renin-Angiotensin System/genetics
  4. Ramachandran V, Ismail P, Stanslas J, Shamsudin N
    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: Renin-Angiotensin System/genetics*
  5. Heidari F, Vasudevan R, Mohd Ali SZ, Ismail P, Arkani M
    Arch Med Res, 2017 Jan;48(1):88-95.
    PMID: 28577874 DOI: 10.1016/j.arcmed.2017.03.003
    BACKGROUNDS AND AIMS: Essential Hypertension (EH) is a common disorder associated with increased cardiovascular morbidity and mortality in Malaysia. To investigate how genetic polymorphisms of the renin-angiotensin-aldosterone system (RAS) influence EH control with angiotensin-converting enzyme inhibitor drugs (ACEI).

    METHODS: A case-control, cross-sectional population-based nested study (n = 142) included hypertensive subjects treated with ACEI drugs, either lisinopril or enalapril (20 mg, once daily) as monotherapy for 24 weeks. In total seven possible polymorphisms of RAS genes were genotyped. The association between those polymorphisms and the changes in blood pressure were observed in the 24 week treatment.

    RESULTS: Statistically significant associations of I, G, T, M and G alleles of ACE (I/D, G2350A), AGT (M235T, T175M and G-6A) respectively were observed in essential hypertensive subjects. The decrease in systolic blood pressure and diastolic blood pressure after 24 weeks of treatment of the patients carrying II, GG, and TT genotypes were greater than the groups carrying DD, AA, MM, MM and GG of I/D, G2350A, M235T, T174M and G-6A genotypes respectively. In contrast, No significant difference was observed between renin gene polymorphisms (Bg/I and MboI) and hypertensives.

    CONCLUSIONS: Although this study shows a possible association of polymorphisms of RAS genes with the risk of non-control of HT in ACEI-treated patients and indicates the importance of all this system's components in regulating HT, it needs to be replicated in other data sources.

    Matched MeSH terms: Renin-Angiotensin System/genetics*
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