关键词: 肌细胞增强因子2A, 启动子, SNP, 转录因子结合位点

Abstract: Objective To explore the influence of the polymorphisms in the promoter of myocyte enhancer factor 2A (MEF2A) on the promoter activity, and the relationship of the polymorphisms with the susceptibility to coronary artery disease (CAD). Methods Forty-four CAD patients and 45 controls were enrolled. The single nucleotide polymorphisms (SNPs) in the promoter of MEF2A and the promoter haplotypes were identified with cloning and Sanger DNA sequencing. The transcription activity of the different promoter haplotypes were determined with dual luciferase reporter system. The frequency of the haplotypes and the homozygosity were compared between CAD and control group. Results Nine SNPs were found, and they combined into 18 haplotypes. H1（16.29%）、H5（17.42%）、H8（16.85%） and H16（28.65%）are the most popular haplotypes, and take 79.21% of the total. H5 and H8 showed the highest transcription activity, and H9 was next, the others were relative weak. Three SNPs, -580(C -> A), －646(G -> T) and -948(C -> T), cause a loss of predicted transcription factor binding site (TFBS). The haplotypes clustered with this 3 SNPs and the frequency was shown as follow: CGC（17.98%）、CGA（3.94%）、TGA（36.51%）、TTC（33.15%）、TTA（3.94%）、TGC（3.37%）、CTC（1.69%）. The haplotype with TGA showed the strongest transcription activity. The homozygosity in CAD group is markedly higher than that in the control group (P < 0.05). Conclusion The SNPs in the promoter of MEF2A may lead to change of TFBS. The different haplotypes have distinct promoter activity, and the homozygosity of MEF2A promoter may contribute to a higher susceptibility to CAD.

Key words: Myocyte enhancer factor 2A, Promoter, SNP, Transcription factor binding site