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Medicine Aug 2022It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is... (Meta-Analysis)
Meta-Analysis
The effect of polymorphisms (M235T and T174M) on the angiotensinogen gene (AGT) in coronary artery disease in the Eastern Asian population: A systematic review and meta-analysis.
BACKGROUND
It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is implicated in CAD susceptibility, but these results contradict those of the other studies with the associations being unclear in the Eastern Asian population. Therefore, meta-analysis was performed to evaluate this relationship.
METHODS
Publication databases were used to search for eligible relevant studies and valid data were extracted from studies meeting the inclusion criteria. Subsequently, odds ratios (ORs) with 95 % confidence intervals (CIs), were used to assess the strength of the association between AGT polymorphism and CAD risk.
RESULTS
Seven eligible studies published only in English were included in the present meta-analysis. In the Eastern Asian population, CAD susceptibility was shown to be related to AGT M235T under the heterozygote model (OR = 0.19). Stratified analysis indicated there was a significant relationship between AGT M235T and CAD risk in China under allelic (OR = 1.34), dominant (OR = 1.43), and heterozygote (OR = 1.62) models. The results showed that the T174M polymorphism was significantly associated with CAD risk in recessive (OR = 2.28) and homozygote (OR = 2.37) models in the Eastern Asian population.
CONCLUSIONS
In the Eastern Asian population, especially the Chinese, the M235T of AGT is associated with CAD susceptibility. The T174M polymorphisms were associated with CAD risk in the Eastern Asian population.
Topics: Angiotensinogen; Asian People; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 36042680
DOI: 10.1097/MD.0000000000029911 -
Cardiology Journal 2022In this recent publication review the authors aimed to collect evidence of impact of nonsynonymous single nucleotide polymorphisms (nsSNP) in the...
In this recent publication review the authors aimed to collect evidence of impact of nonsynonymous single nucleotide polymorphisms (nsSNP) in the renin-angiotensin-aldosterone system on patients' phenotype not only regarding arterial hypertension and its complications, but also the impact on other diseases of interest outside the field of cardiovascular medicine. PubMed database records published between 2017-2020 were searched and all positive case-control studies or positive studies with human DNA were selected. The search identified 104 articles, of which 22 were included on the basis of the inclusion criteria. This paper presents the impact of 44 nsSNPs in panels for genes of renin, angiotensinogen, angiotensin-converting enzyme, angiotensin receptor and aldosterone on the clinical picture of investigated cohorts or on the peptide-protein interactions as consequence of nsSNPs. Genetic variability in nsSNPs of the RAAS is involved in the pathogenesis of arterial hypertension and its complications, and surprisingly also in the pathogenesis of conditions not associated with elevated blood pressure, like neoplasms or inflammatory diseases.
Topics: Humans; Renin-Angiotensin System; Polymorphism, Single Nucleotide; Renin; Aldosterone; Hypertension
PubMed: 34060646
DOI: 10.5603/CJ.a2021.0055 -
American Journal of Obstetrics and... Feb 2022There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying...
There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.
Topics: Antibodies, Monoclonal; Antioxidants; Antithrombin III; Biological Products; Blood Component Removal; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Metformin; Micronutrients; Placenta Growth Factor; Plant Extracts; Pravastatin; Pre-Eclampsia; Pregnancy; Proton Pump Inhibitors; RNA, Small Interfering; Recombinant Proteins; Sulfasalazine; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32946849
DOI: 10.1016/j.ajog.2020.09.014 -
Anatolian Journal of Cardiology Mar 2019M235T polymorphism of the angiotensinogen (AGT) gene has been linked with cardiovascular disease (CVD). The aim of this meta-analysis was to investigate whether combined... (Meta-Analysis)
Meta-Analysis
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.
Topics: Angiotensinogen; Asian People; Cardiovascular Diseases; Case-Control Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic
PubMed: 30930452
DOI: 10.14744/AnatolJCardiol.2019.75282