The Pro279Leu variant in the transcription factor MEF2A is associated with myocardial infarction

González, Pelayo; García-Castro, Mónica; Reguero, Julián R.; Batalla, Alberto; Ordoñez, Angel González; Palop, Ramón Lopéz; Lozano, Íñigo; Montes, María Guadalupe; Álvarez, Victoria; Coto, Eliécer

doi:10.1136/jmg.2005.035071

Cited by 54 publications

(60 citation statements)

References 12 publications

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“…15 However, this variant was not associated with MI in our much lager sample of patients with nonfamilial MI and displayed no association with MI in the abovementioned Spanish MI population. 14 Our findings are in line with the results obtained by Weng et al 12 and Horan et al 24 Weng and colleagues found no causative MI mutation in 300 CAD cases, and Horan and associates failed to detect the 21-bp deletion described by Wang et al 10 in 1481 individuals with a positive family history for ischemic heart disease. Similarly, we found no disease-causing mutation in our 23 extended MI families, suggesting that MEF2A mutations are responsible for only a relatively small proportion of familial MI cases.…”

Section: Discussionsupporting

confidence: 91%

“…11 The role of MEF2A was subsequently studied in a few small molecular genetic association studies on sporadic MI patients, producing inconsistent results. [12][13][14][15] Thus far, no families with autosomal-dominant inheritance of MI were available for genetic investigations, so the MEF2A gene was never analyzed in the specific context that initially allowed the identification of the genetic variant. To further clarify the role of MEF2A, we performed a comprehensive analysis in both familial and sporadic MI cases and in exceptional families with up to 22 affected members with MI.…”

Section: Clinical Perspective P 191mentioning

confidence: 99%

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Lack of Association Between the MEF2A Gene and Myocardial Infarction

Lieb

Mayer²,

König³

et al. 2008

Circulation

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Background— Coronary artery disease (CAD) and myocardial infarction (MI) are caused in part by genetic factors. Recently, the MEF2A gene was linked to MI/CAD in a single pedigree with autosomal-dominant pattern of inheritance. In addition, genetic variants within the gene have been associated with MI in case-control settings, producing inconsistent results. Methods and Results— The MEF2A gene was sequenced in MI patients from 23 MI families (≥5 affected members per family), but no mutation was identified in any of these extended families. Moreover, the Pro279Leu variant in exon 7 was analyzed in 1181 unrelated MI patients with a positive family history for MI/CAD, in 533 patients with sporadic MI, and in 2 control populations (n=1021 and n=1055), showing no evidence for association with MI/CAD. In addition, a (CAG)n repeat in exon 11 was genotyped in 543 sporadic MI patients and in 1190 controls without evidence for association with MI. Finally, analyzing 11 single-nucleotide polymorphisms from the GeneChip Mapping 500K Array, genotyped in 1644 controls and 753 cases, failed to provide evidence for association (region-wide P =0.23). Conclusions— Studying independent samples of >1700 MI patients, 2 large control populations, and multiple families with apparently mendelian inheritance of the disease, we found no evidence for any linkage or association signal in the MEF2A gene.

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Section: Discussionsupporting

confidence: 91%

Section: Clinical Perspective P 191mentioning

confidence: 99%

Lack of Association Between the MEF2A Gene and Myocardial Infarction

Lieb

Mayer²,

König³

et al. 2008

Circulation

View full text Add to dashboard Cite

show abstract

“…All 316 patients agreed to participate in a research on the genetic factors involved in MI, and none refused to participate. 23,24 Patients were defined as hypertensives if they had a documented history of hypertension, with a systolic blood pressure >140 mmHg in more than one determination. Patients with a history of hypercholesterolaemia or showing total cholesterol concentrations >250 mg/dl were defined as hypercholesterolaemics.…”

Section: Methodsmentioning

confidence: 99%

Role of the CDKN1A/p21, CDKN1C/p57, and CDKN2A/p16 Genes in the Risk of Atherosclerosis and Myocardial Infarction

Rodríguez

Coto²,

Reguero³

et al. 2007

Cell Cycle

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“…Also, expression of dominant-negative isoforms of MEF2 predicted to inhibit all MEF2 function resulted in the inhibition of skeletal myogenesis in mammalian cells in vitro (40) and in interference in cardiac development in vivo (23). Finally, a point mutation in the human gene encoding MEF2A is associated with susceptibility to cardiac disease (19). These studies present a strong argument for the importance of MEF2 proteins in muscle development and disease.…”

mentioning

confidence: 89%

Myocyte Enhancer Factor 2 and Chorion Factor 2 Collaborate in Activation of the Myogenic Program in Drosophila

Kelly

Bryantsev

Cripps

2008

Molecular and Cellular Biology

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The process of myogenesis requires the coordinated activation of many structural genes whose products are required for myofibril assembly, function, and regulation. Although numerous reports have documented the importance of the myogenic regulator myocyte enhancer factor 2 (MEF2) in muscle differentiation, the interaction of MEF2 with cofactors is critical to the realization of muscle fate. We identify here a genomic region required for full MEF2-mediated activation of actin gene expression in Drosophila, and we identify the zinc finger transcriptional regulator chorion factor 2 (CF2) as a factor functioning alongside MEF2 via this region. Furthermore, although both MEF2 and CF2 can individually activate actin gene expression, we demonstrate that these two factors collaborate in regulating the Actin57B target gene in vitro and in vivo. More globally, MEF2 and CF2 synergistically activate the enhancers of a number of muscle-specific genes, and loss of CF2 function in vivo results in reductions in the levels of several muscle structural gene transcripts. These findings validate a general importance of CF2 alongside MEF2 as a critical regulator of the myogenic program, identify a new regulator functioning with MEF2 to control cell fate, and provide insight into the network of regulatory events that shape the developing musculature.

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The Pro279Leu variant in the transcription factor MEF2A is associated with myocardial infarction

Abstract: The 279Leu allele appears to be a genetic risk factor for CAD/MI in the population studied. This effect could be the result of a reduced transcriptional activity on MEF2A with 279Leu.

Cited by 54 publications

References 12 publications

Lack of Association Between the MEF2A Gene and Myocardial Infarction

Lack of Association Between the MEF2A Gene and Myocardial Infarction

Role of the CDKN1A/p21, CDKN1C/p57, and CDKN2A/p16 Genes in the Risk of Atherosclerosis and Myocardial Infarction

Myocyte Enhancer Factor 2 and Chorion Factor 2 Collaborate in Activation of the Myogenic Program in Drosophila

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