MEF2A sequence variants and coronary artery disease: a change of heart?
Rare mutations in MEF2A have been proposed as a cause of coronary artery disease (CAD) and myocardial infarction (MI). In this issue of the JCI, Pennacchio and colleagues report sequencing MEF2A in 300 patients with premature CAD and in controls. Only 1 CAD patient was found to carry a missense mutation not found in controls. The specific 21-bp deletion in MEF2A previously proposed as causal for CAD and/or MI was observed in unaffected individuals and did not segregate with CAD in families. These results do not support the hypothesis that mutations in MEF2A are a cause of CAD and/or MI but do illustrate general principles regarding the difficulty of connecting genetic variation to common diseases.
Altshuler
David
D
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. altshuler@molbio.mhg.harvard.edu
Hirschhorn
Joel N
JN
D002884:Chromosomes, Human, Pair 15; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005820:Genetic Testing; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D020125:Mutation, Missense; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology; D018006:Myogenic Regulatory Factors; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors