Lack of Association between the MEF2A Gene and Coronary Artery Disease in Iranian Families

Authors

1 School of Biology, University College of Science, Tehran, Iran

2 Tehran University of Medical Sciences, Tehran, Iran

Abstract

Objective(s):  Coronary artery disease (CAD) which may lead to myocardial infarction (MI) is a complex one. Great effort has been devoted to identification of genes that increase susceptibility to CAD or provide protection. A 21-bp deletion in the MEF2A gene, which encodes a member of the myocyte enhancer factor 2 family of transcription factors, has been reported in patients of a single pedigree that exhibited autosomal-dominant inheritance of CAD. Subsequent analysis of genetic variants within the gene in CAD and MI case-control settings produced inconsistent results. Here, we aimed at assessing the contribution of MEF2A to CAD in a cohort of Iranian CAD patients.
Materials and Methods:Exon 11 of MEF2A wherein the above mentioned 21-bp deletion and a polyglutamine (CAG)n polymorphism are positioned was sequenced by the dideoxy-nucleotide termination protocol.  In 52 CAD patients from 12 families (3-7 affected members per family) and 76 Iranian control individuals. All exons of the gene were sequenced in 10 patients and 10 controls.
Results:The 21-bp deletion was observed neither among the patients nor the control individuals. Four alleles of the polyglutamine (CAG)n polymorphism were found, but there were no significant differences in allelic frequencies between patients and controls. Sequencing of all exons of MEF2A revealed the presence of 12 novel sequence variations in introns and flanking regions of MEF2A gene, not associated with disease status.
Conclusion: Our data do not support a role for MEF2A in coronary artery disease in the Iranian patients studied

Keywords


1. Wang Q. Advances in the genetics basis of coronary artery disease. Curr Atheroscler Rep 2005; 7:235–241.

2. Luo AK, Jefferson BK, Garcia MJ, Ginsburg JS, Topol EJ. Challenges in the phenotypic characterisation of patients in genetic studies of coronary artery disease. J Med Genet 2007; 44:161-165.

3. Gonzalez P, Garcia-Castro M, Reguero JR, Batalla A, Ordonez AG, Palop RL, et al. The Pro279Leu variant in the transcription factor MEF2A is associated with myocardial infarction. J Med Genet 2006; 43:167-169.

4. Wang L, Fan C, Topol SE, Topol EJ, Wang Q. Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Science 2003; 302:1578-1581.

5. YT Y. Distinct domains of myocyte enhancer binding factor-2A determining nuclear localization and cell type-specific transcriptional activity. J Biol Chem  1996; 271:24675–24683.

 6. Weng L, Kavalar N, Ustaszewska A. Pennacchio LA. Lack of MEF2A mutations in coronary artery disease. J Clin Invest  2005; 115:1016–1020.

7. Altshuler D, Hirschhorn JN. MEF2A sequence variants and coronary artery disease: a change of heart? Nat Genet 2005; 115:831-833.

8. Bhagavatula MR, Fan C, Shen GQ, Cassano J, Plow EF, Topol EJ, et al. Transcription factor MEF2A mutations in patients with coronary artery disease. Hum Mol Genet  2004; 13:3181–3188.

9. Kajimoto K, Shioji K, Tago N, Tomoike H, Nonogi H, Goto Y, et al. Assessment of MEF2A mutations in myocardial infarction in Japanese patients. Circ J  2005; 69:1192–1195.

10. Horan PG, Allen AR, Hughes AE, Patterson CC, Spence M, McGlinchey PG, et al. Lack of MEF2A Delta7aa mutation in Irish families with early onset ischaemic heart disease, a family based study. BMC Med Genet  2006; 27:65.

11. Li J, Yang JG, Li W, Du R, Gui L, Tian L, et al. Study on novel mutations of MEF2A gene in Chinese patients with coronary artery disease. Zhonghua Yi Xue Yi Chuan Xue Za Zhi  2006; 23:265–268.

12. Han Y, Yang Y, Zhang X, Yan C, Xi S, Kang J. Relationship of the CAG repeat polymorphism of the MEF2A gene and coronary artery disease in a Chinese population. Clin Chem Lab Med 2007; 45:987–992.

13. Lieb W, Mayer B, Ko¨nig IR, Borwitzky I, Go¨tz A, Kain S, et al. Lack of association between the MEF2A gene and myocardial infarction. Circulation  2008; 117:185–191.

14. Liu Y, Niu W, Wu Z, Su X, Chen Q, Lu L, et al. Variants in Exon 11 of MEF2A Gene and Coronary Artery Disease: Evidence from a Case-Control Study, Systematic Review, and Meta-Analysis. PloS ONE 2012; 7:2, e31406.

15. Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 2007; 316:1491–1493.

16. McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR , et al. Lessons from studying monogenic disease for common disease. Hum Mol Genet  2006; 15: R67–R74.

17. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, et al. Genomewide association analysis of coronary artery disease. N Engl J Med  2007; 357:443– 453.

18. Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC. A common allele on chromosome 9 associated with coronary heart disease. Science 2007; 316:1488 –1491.