Association of Mef2a gene polymorphisms in early onset of coronary artery disease of south Indian cohort

Maddhuri, Sailaja; Gudala, Suresh; Lakkaraju, Chandana; Malempati, Amaresh Rao; Nallari, N. Pratibha; Mundluru, Hema Prasad

doi:10.1016/j.mgene.2017.10.001

Cited by 3 publications

(8 citation statements)

References 27 publications

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“…Clinical data on traditional CAD risk factors such as hypertension, hypercholesterolemia, and diabetes are available. This is consistent with the findings of Maddhuri et al (2018) reported that the risk of total cholesterol and LDL-C were considerably greater in patients than in healthy controls (p<0.001), but high-density level-C was higher in normal than in experimental groups [6]. Also, it was found that vegan diets may improve health and reduce the risk of CAD and heart failure [14].…”

Section: Discussionsupporting

confidence: 91%

“…This validates the findings of Foroughmand et al (2014) who investigated the association of MEF2A gene polymorphisms with coronary artery disease [19]. Also, Maddhuri et al (2018) found that the CT and TT genotypes were predominant in CAD with two and singlefold increased risk of CAD, respectively [6].…”

Section: Discussionsupporting

confidence: 86%

“…MEF2A mutations and deletions alter the endothelial transcriptional profile, rendering the endothelium dysfunctional and more vulnerable to inflammatory particle invasion such as LDLs, monocytes, and macrophages. These macrophages are crucial for lipid accumulation, cytokine production, and growth factor release, which promote the proliferation of smooth muscle cells, and lead to the collapse of the fibrous cap, plaque development, and atherosclerosis [6].…”

Section: Introductionmentioning

confidence: 99%

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A Study of transcription factor MEF2A gene polymorphisms in patients with coronary artery disease

Kazhal Muhammad Sulaiman

2024

Cell Mol Biol (Noisy-le-grand)

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MEF2A (myocyte enhancer factor-2A) is a transcription factor of the MEF2 family. It has been recognized as the cause of coronary artery disease in the absence of any other clinical characteristic. It is involved in vascular development and is most commonly found in the coronary artery endothelium. The goal of this case-control study was to see if there was a link between polymorphisms in the MEF2A gene and coronary artery disease. A case-control study was carried out to look into the possible significance of MEF2A polymorphisms as a risk factor for coronary artery disease. This research included 225 patients and 225 healthy controls. A biochemical examination was carried out to evaluate the risk factors for developing this condition. The polymorphisms of Mef2A (1250 C > T in exon 8 and 452 G > T, 481 A > G in exon 11) were found using the PCR-RFLP technique. All identified risk variables, such as hypercholesterolemia, diabetes mellitus, and hypertriglyceridemia, were shown to be statistically significant in the current study for coronary artery disease occurrence. The most polymorphisms were found in MEF2A 1250 C > T, MEF2A 452 G > T, and MEF2A 481 A > G. The genotyping results for MEF2A 1250, MEF2A 452, and MEF2A 481 were (X 2 = 2.985; P = 0.235), (X 2 = 4.371; P = 0.112), and (X 2 = 4.025; P = 0.134), respectively. In conclusion, we identified a much higher incidence of MEF2A in people with coronary artery disease, and MEF2A may play a crucial role in cardiovascular pathophysiology. Patients and controls had considerably different genetics and frequency of alleles.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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A Study of transcription factor MEF2A gene polymorphisms in patients with coronary artery disease

Kazhal Muhammad Sulaiman

2024

Cell Mol Biol (Noisy-le-grand)

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“…Since then, many researchers have extensively studied the correlation between MEF2A genetic variation and coronary artery disease (CAD). However, the results were disappointing as no genetic variation tightly associated with CAD has been found in the MEF2A gene region [10–16]. Recently, a novel 6-bp deletion in the 11 th exon of MEF2A has been found to be closely related to early-onset CAD in a Chinese family [17].…”

Section: Introductionmentioning

confidence: 99%

Myocyte enhancer factor 2A delays vascular endothelial cell senescence by activating the PI3K/p-Akt/SIRT1 pathway

Liu

Wang

Jiang

et al. 2019

Aging

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Myocyte enhancer factor 2A (MEF2A) dysfunction is closely related to the occurrence of senile diseases such as cardiocerebrovascular diseases, but the underlying molecular mechanism is unclear. Here, we studied the effects of MEF2A on the senescent phenotype of vascular endothelial cells (VEC) and downstream signaling pathway, and the association between plasma MEF2A levels and coronary artery disease (CAD). Results showed that MEF2A silencing promoted cell senescence and down-regulated PI3K/p-AKT/Sirtuin 1 (SIRT1) expression. MEF2A overexpression delayed cell senescence and up-regulated PI3K/p-AKT/SIRT1. Hydrogen peroxide (H 2 O 2 ) treatment induced cellular senescence and down-regulated the expression of MEF2A and PI3K/p-AKT/SIRT1. MEF2A overexpression inhibited cellular senescence and the down-regulation of PI3K/p-AKT/SIRT1 induced by H 2 O 2 . Further study revealed that MEF2A directly up-regulated the expression of PIK3CA and PIK3CG through MEF2 binding sites in the promoter region. Pearson correlation and logistic regression analysis showed that the plasma level of MEF2A was negatively correlated with CAD, and with age in the controls. These results suggested that MEF2A can directly up-regulate PI3K gene expression, and one of the molecular mechanisms of delaying effect of MEF2A on VEC cell senescence was SIRT1-expression activation through the PI3K/p-Akt pathway. Moreover, the plasma MEF2A levels may be a potential biomarker for CAD risk prediction.

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“…Another study has reported that a novel 6 bp deletion in exon 11 of MEF2A is closely associated with premature CAD [ 8 ]. Nonsynonymous mutation or variation in the number of CAG or CCG repeats is correlated with susceptibility to CAD in some populations [ 9 , 10 ]. However, the roles of MEF2A variants in CAD are controversial because not all studies can show the association between these variants and CAD [ 11 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells

et al. 2019

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BackgroundMyocyte enhancer factor 2A (MEF2A) plays an important role in cell proliferation, differentiation and survival. Functional deletion or mutation in MEF2A predisposes individuals to cardiovascular disease mainly caused by vascular endothelial dysfunction. However, the effect of the inhibition of MEF2A expression on human coronary artery endothelial cells (HCAECs) is unclear. In this study, expression of MEF2A was inhibited by specific small interference RNA (siRNA), and changes in mRNA profiles in response to MEF2A knockdown were analyzed using an Agilent human mRNA array.ResultsSilencing of MEF2A in HCAECs accelerated cell senescence and suppressed cell proliferation. Microarray analysis identified 962 differentially expressed genes (DEGs) between the MEF2A knockdown group and the negative control group. Annotation clustering analysis showed that the DEGs were preferentially enriched in gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to proliferation, development, survival, and inflammation. Furthermore, 61 of the 578 downregulated DEGs have at least one potential MEF2A binding site in the proximal promoter and were mostly enriched in the GO terms “reproduction” and “cardiovascular.” The protein–protein interaction network analyzed for the downregulated DEGs and the DEGs in the GO terms “cardiovascular” and “aging” revealed that PIK3CG, IL1B, IL8, and PRKCB were included in hot nodes, and the regulation of the longevity-associated gene PIK3CG by MEF2A has been verified at the protein level, suggesting that PIK3CG might play a key role in MEF2A knockdown induced HCAEC senescence.ConclusionsMEF2A knockdown accelerates HCAEC senescence, and the underlying molecular mechanism may be involved in down-regulation of the genes related with cell proliferation, development, inflammation and survival, in which PIK3CG may play a key role.Electronic supplementary materialThe online version of this article (10.1186/s12867-019-0125-z) contains supplementary material, which is available to authorized users.

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Association of Mef2a gene polymorphisms in early onset of coronary artery disease of south Indian cohort

Cited by 3 publications

References 27 publications

A Study of transcription factor MEF2A gene polymorphisms in patients with coronary artery disease

A Study of transcription factor MEF2A gene polymorphisms in patients with coronary artery disease

Myocyte enhancer factor 2A delays vascular endothelial cell senescence by activating the PI3K/p-Akt/SIRT1 pathway

MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells

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