| 1580549 | Lack of MEF2A mutations in coronary artery disease. | Weng L, etal., J Clin Invest. 2005 Apr;115(4):1016-20. | Mutations in MEF2A have been implicated in an autosomal dominant form of coronary artery disease (adCAD1). In this study we sought to determine whether severe mutations in MEF2A might also explain sporadic cases of coronary artery disease (CAD). To do this, we resequenced the coding sequence and splice sites of MEF2A in approximately 300 patients with premature CAD and failed to find causative mutations in the CAD cohort. However, we did identify the 21-bp MEF2A coding sequence deletion originally implicated in adCAD1 in 1 of 300 elderly control subjects without CAD. Further screening of approximately 1,500 additional individuals without CAD revealed 2 more subjects with the MEF2A 21-bp deletion. Genotyping of 19 family members of the 3 probands with the 21-bp deletion in MEF2A revealed that the mutation did not cosegregate with early CAD. These studies support that MEF2A mutations are not a common cause of CAD in white people and argue strongly against a role for the MEF2A 21-bp deletion in autosomal dominant CAD. | 15841183 | 2005-08-01 |
| 11353606 | Association of MEF2A gene 3'UTR mutations with coronary artery disease. | Huang XC and Wang W, Genet Mol Res. 2015 Sep 21;14(3):11073-8. doi: 10.4238/2015.September.21.20. | Association of variants in the myocyte enhancer factor 2A (MEF2A) gene and the risk of coronary artery disease (CAD) has drawn much attention but remains controversial. We hypothesized that the 3'-untranslated region (3'-UTR) of this gene could harbor functional ly relevant nucleotide changes. Here, we assessed the association between single nucleotide polymorphisms (SNPs) in the 3'-UTR of MEF2A and CAD in the Chinese Han population. A case-control study of 236 CAD patients and 278 controls was carried out. The four target SNPs were genotyped using a multiplex PCR-ligase detection reaction method. Logistic regression under three genetic models was used to analyze the association between target SNPs and the risk of CAD. Associations were detected between two SNPs (rs325380, rs897074) and CAD; however, after Bonferroni's correction, these associations were not deemed significant. A further haplotype study indicated that a 'TA' haplotype carrier of rs325380-rs325381 was associated with CAD risk. Our study thus indicates that variants in the 3'-UTR of MEF2A are associated with CAD in a Chinese Han population. | 26400337 | 1000-07-01 |
| 598120614 | Mutation of MEF2A in an inherited disorder with features of coronary artery disease. | Wang L, etal., Science. 2003 Nov 28;302(5650):1578-81. doi: 10.1126/science.1088477. | The early genetic pathway(s) triggering the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) remain largely unknown. Here, we describe an autosomal dominant form of CAD/MI (adCAD1) that is caused by the deletion of seven amino acids in transcription factor MEF2A nt-weight:700;'>MEF2A. The deletion disrupts nuclear localization of MEF2A, reduces MEF2A-mediated transcription activation, and abolishes synergistic activation by MEF2A and by the transcription factor GATA-1 through a dominant-negative mechanism. The MEF2A protein demonstrates strong expression in the endothelium of coronary arteries. These results identify a pathogenic gene for a familial vascular disease with features of CAD and implicate the MEF2A signaling pathway in the pathogenesis of CAD/MI. | 14645853 | 2003-11-28 |
| 11079547 | Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo. | Latchney SE, etal., FASEB J. 2015 Dec;29(12):5059-71. doi: 10.1096/fj.15-275651. Epub 2015 Aug 18.id: 23312806 Error occurred: The following PMID is not available: 23312806 | Myocyte enhancer factor (Mef)-2 transcription factors are implicated in activity-dependent neuronal processes during development, but the role of MEF2 in neural stem/progenitor cells (NSPCs) in the adult brain is unknown. We used a transgenic mouse in which Mef2a >, -c, and -d were inducibly deleted in adult nestin-expressing NSPCs and their progeny. Recombined cells in the hippocampal granule cell layer were visualized and quantified by yellow fluorescent protein (YFP) expression. In control mice, postmitotic neurons expressed Mef2a, -c, and -d, whereas type 1 stem cells and proliferating progenitors did not. Based on this expression, we hypothesized that Mef2a, -c, and -d deletion in adult nestin-expressing NSPCs and their progeny would result in fewer mature neurons. Control mice revealed an increase in YFP(+) neurons and dendrite formation over time. Contrary to our hypothesis, inducible Mef2 KO mice also displayed an increase in YFP(+) neurons over time-but with significantly stunted dendrites-suggesting an uncoupling of neuron survival and dendritogenesis. We also found non-cell-autonomous effects after Mef2a, -c, and -d deletion. These in vivo findings indicate a surprising functional role for Mef2a, -c, and -d in cell- and non-cell-autonomous control of adult hippocampal neurogenesis that is distinct from its role during development. | 26286136 | 2015-05-01 |
| 11537242 | Inhibition of MEF2A prevents hyperglycemia-induced extracellular matrix accumulation by blocking Akt and TGF-beta1/Smad activation in cardiac fibroblasts. | Chen X, etal., Int J Biochem Cell Biol. 2015 Dec;69:52-61. doi: 10.1016/j.biocel.2015.10.012. Epub 2015 Oct 23. | Myocyte enhancer factor 2A (MEF2A) functions in muscle-specific and/or growth factor-related transcription and is involved in cell growth, survival, and apoptosis. To evaluate the role of this transcription factor in cardiac fibroblasts (CFs) in diabetes mellitu s, we performed a series of in vitro and in vivo experiments. We used short hairpin RNA (shRNA) to inhibit the expression of MEF2A in CFs in vitro. Inhibition of MEF2A significantly reduced hyperglycemia-induced CF proliferation and migration, myofibroblast differentiation, matrix metalloproteinase (MMP) activities, and collagen production. Furthermore, MEF2A inhibition attenuated HG-induced activation of the mitogen-activated protein kinase (MAPK), Akt, and TGF-beta1/Smad signaling pathways. For in vivo analysis in a mouse model, type-1 diabetes was induced by streptozotocinand MEF2A expression was knocked down by myocardial injection with lentivirus carrying shRNA-MEF2A. Cardiac function was assessed by echocardiography. Total collagen deposition was assessed by Masson's trichrome and Picrosirius red staining. Knockdown of MEF2A ameliorated diabetes-induced cardiac dysfunction and collagen deposition. Our study suggests that inhibition of MEF2A could alleviate HG-induced extracellular matrix accumulation by blocking the activation of Akt and TGF-beta1/Smad signaling pathway in CFs. Thus, inhibition of MEF2A has therapeutic potential in the treatment of diabetic-induced cardiac remodeling. | 26482596 | 2015-09-01 |
| 11537933 | Linkage and whole genome sequencing identify a locus on 6q25-26 for formal thought disorder and implicate MEF2A regulation. | Thygesen JH, etal., Schizophr Res. 2015 Dec;169(1-3):441-6. doi: 10.1016/j.schres.2015.08.037. Epub 2015 Oct 1. | Formal thought disorder is a major feature of schizophrenia and other psychotic disorders. It is heritable, found in healthy relatives of patients with schizophrenia and other mental disorders but knowledge of specific genetic factors is lacking. The aim of this study was to search for biologically relevant high-risk variants. Formal thought disorder was assessed in participants in the Copenhagen Schizophrenia Linkage Study (N=236), a unique high-risk family study comprised of six large pedigrees. Microsatellite linkage analysis of formal thought disorder was performed and subsequent haplotype analysis of the implicated region using phased microsatellite and SNP genotypes. Whole genome sequencing (N=3) was used in the attempt to identify causative variants in the linkage region. Linkage analysis of formal thought disorder resulted in a single peak at chromosome 6(q26-q27) centred on marker D6S1277, with a maximum LOD score of 4.0. Phasing and fine mapping of the linkage peak identified a 5.5Mb haplotype (chr6:162242322-167753547, hg18) in 31 individuals, all belonging to the same pedigree sharing the haplotype from a common ancestor. The haplotype segregated with increased total thought disorder index score (P=4.9 x 10(-5)) and qualitatively severe forms of thought disturbances. Whole genome sequencing identified a novel nucleotide deletion (chr6:164377205 AG>A, hg18) predicted to disrupt the potential binding of the transcription factor MEF2A. The MEF2A binding site is located between two genes previously reported to associate with schizophrenia, QKI (HGNC:21100) and PDE10A (HGNC:8772). The findings are consistent with MEF2A deregulation conferring risk of formal thought disorder. | 26421691 | 2015-10-01 |
