Variants in Exon 11 of MEF2A Gene and Coronary Artery Disease: Evidence from a Case-Control Study, Systematic Review, and Meta-Analysis

BACKGROUND Coronary 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 FINDINGS We 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/SIGNIFICANCE Our 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.