Abstract
BackgroundCoronary artery disease (CAD) is the most common heart disease worldwide. Association of CAD with variants in the myocyte enhancer factor 2A (MEF2A) gene, the first identified CAD-causing gene, has attracted special attention but the results are controversial. We aimed to evaluate this genetic association via a case-control study and meta-analysis.Methodology/Principal FindingsWe performed a case-control association study to investigate the relationship between variations in exon 11 of MEF2A gene and CAD in 1045 sporadic patients and 1008 controls enrolled angiographically among southern Chinese population, and then the data from this study were compared and discussed in a systematic review and meta-analysis with all available published studies on MEF2A gene and CAD. In total, eight variants were identified (21-bp deletion, CAG repeats, CCG repeats, a CCA deletion and four SNPs). No significant link was observed between the common (CAG)n polymorphism and CAD, whereas the rare 21-bp deletion was detected only in five affected individuals. The meta-analysis of (CAG)n polymorphism and CAD risk, including nine studies with 3801 CAD patients and 4020 controls, also provided no convincing evidence for the genetic association, even upon stratification by race (mainly Whites and Chinese). However, the 21-bp deletion was regarded as a potentially logical, albeit undetermined, candidate for CAD in the following systematic review.Conclusions/SignificanceOur findings failed to demonstrate a correlation between (CAG)n polymorphism with CAD, however, we concluded that the rare 21-bp deletion might have a more compelling effect on CAD than the common (CAG)n polymorphism, and MEF2A genetic variant might be a rare but specific cause of CAD/MI.
Highlights
Coronary artery disease (CAD) is a common complex disorder resulting from both genetic and environmental influences [1,2], and it has become a major cause of death and disability in China
We verified eight variants in myocyte enhancer factor 2A (MEF2A) exon 11 and found that the most conspicuously heterogeneous variant was the (CAG)n polymorphism, while the other seven were all downstream of this polymorphism within 100 bp. Such intense variation in the context of a single exon led us to explore the link of MEF2A genetic polymorphisms to CAD/myocardial infarction (MI)
We carried out a rigorously-designed case-control association study focusing on MEF2A exon 11 in southern Chinese and reviewed all available information regarding the relationship between this genetic hotspot and sporadic CAD/ MI from the literature
Summary
Coronary artery disease (CAD) is a common complex disorder resulting from both genetic and environmental influences [1,2], and it has become a major cause of death and disability in China. In vitro functional analysis indicated that the 21-bp deletion disrupted the nuclear localization of mature protein and decreased MEF2Ainduced transcriptional activation. This genetic imperfection might lead to a defective or abnormal vascular endothelium, which could promote the genesis of atherosclerotic plaque or thrombosis and influence the whole process of atherogenesis [11]. Association of CAD with variants in the myocyte enhancer factor 2A (MEF2A) gene, the first identified CAD-causing gene, has attracted special attention but the results are controversial. We aimed to evaluate this genetic association via a case-control study and meta-analysis
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