Structural changes in exon 11 of MEF2A are not related to sporadic coronary artery disease in Han Chinese population

• Published in: European journal of clinical investigation 2010-08, Vol.40 (8), p.669-677
• Main Authors: Dai, Da-Peng, Zhou, Xiao-Yang, Xiao, Yao, Xu, Feng, Sun, Fu-Cheng, Ji, Fu-Sui, Zhang, Zhi-Xin, Hu, Ji-Hong, Guo, Jian, Zheng, Jun-De, Dong, Jia-Mei, Zhu, Wei-Guo, Shen, Yan, Qian, Yi-Jian, He, Qing, Cai, Jian-Ping
• Format: Article
• Language: English
• Subjects: Aged; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Cardiology. Vascular system; Coronary artery disease; Coronary Artery Disease - genetics; Coronary heart disease; Exons - genetics; Female; General aspects; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Heart; Humans; MADS Domain Proteins - genetics; Male; Medical sciences; MEF2 Transcription Factors; MEF2A; Middle Aged; Mutation; Myogenic Regulatory Factors - genetics; Sequence Analysis, DNA; subcellular localization; transcriptional activation; trinucleotide (CAG) repeat
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2010.02307.x

Eur J Clin Invest 2010; 40 (8): 669–677 Background  A mutation in MEF2A (myocyte enhancer factor‐2A) had been reported to be the first gene linked directly to coronary artery disease (CAD). However, an opposing opinion was proposed recently that MEF2A mutations are not a common cause of sporadic CAD. In this study, we screened exon 11 of the MEF2A gene in people of the Han nationality in China and finished some functional analysis of found variations. Materials and methods  A gene structural investigation of MEF2A in 257 CAD patients and 154 control individuals were developed in this study. Subsequently, typical MEF2A variations were cloned and expressed in HeLa or 293T cell line to illustrate whether found structure changes could influence the main biological functions of these proteins. At last, another set of gene structural screen was initialized to get more reliable conclusions. Results  Totally 16 different variations were detected in exon 11 of this gene in the first set of gene structural screen. By cloning and expressing typical MEF2A proteins in cultured cells, all the acquired MEF2A variations had transcriptional activation capabilities and subcellular localization patterns similar to those of the wild‐type protein. Further larger scale genetic screening also revealed that the reported genetic variations of MEF2A did not differ significantly between CAD patients and healthy controls. Conclusions  Our results reveal that structural changes of exon 11 in MEF2A are not involved in sporadic CAD in the Han population of China.