Novel 6-bp deletion in MEF2A linked to premature coronary artery disease in a large Chinese family

Xu,Dong‑Ling; Tian,Hong‑Liang; Cai,Wei‑Li; Zheng,Jie; Gao,Min; Zhang,Ming‑Xiang; Zheng,Zhao-Tong; Lu,Qing‑Hua

doi:10.3892/mmr.2016.5297

Novel 6-bp deletion in MEF2A linked to premature coronary artery disease in a large Chinese family

Authors:
- Dong‑Ling Xu
- Hong‑Liang Tian
- Wei‑Li Cai
- Jie Zheng
- Min Gao
- Ming‑Xiang Zhang
- Zhao-Tong Zheng
- Qing‑Hua Lu
View Affiliations

Affiliations: Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Cardiology, The Third Hospital of Jinan, Jinan, Shandong 250021, P.R. China
Published online on: May 18, 2016 https://doi.org/10.3892/mmr.2016.5297
Pages: 649-654
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to identify the genetic defect responsible for familial coronary artery disease/myocardial infarction (CAD/MI), which exhibited an autosomal dominant pattern of inheritance, in an extended Chinese Han pedigree containing 34 members. Using exome and Sanger sequencing, a novel 6‑base pair (bp) ‘CAGCCG’ deletion in exon 11 of the myocyte enhancer factor 2A (MEF2A) gene was identified, which cosegregated with CAD/MI cases in this family. This 6‑bp deletion was not detected in 311 sporadic cases of premature CAD/MI or in 323 unrelated healthy controls. Determination of a genetic risk profile has a key role in understanding the pathogenesis of CAD and MI. Among the reported risk‑conferring genes and their variants, mutations in MEF2A have been reported to segregate with CAD/MI in Caucasian families. Causative missense mutations have also been detected in sporadic CAD/MI cases. However, this suggested genetic linkage is controversial, since it could not be confirmed by ensuing studies. The discovery of a novel MEF2A mutation in a Chinese family with premature CAD/MI suggests that MEF2A may have a significant role in the pathogenesis of premature CAD/MI. To better understand this association, further in vitro and in vivo studies are required.

View Figures

View References

1	Wang L, Fan C, Topol ES, Topol EJ and Wang Q: Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Science. 302:1578–1581. 2003. View Article : Google Scholar : PubMed/NCBI
2	González P, García-Castro M, Reguero JR, Batalla A, Ordóñez AG, Palop RL, Lozano I, Montes M, Alvarez V and Coto E: The Pro279Leu variant in the transcription factor MEF2A is associated with myocardial infarction. J Med Genet. 43:167–169. 2006. View Article : Google Scholar
3	Lieb W, Mayer B, König IR, Borwitzky I, Götz A, Kain S, Hengstenberg C, Linsel-Nitschke P, Fischer M, Döring A, et al: Lack of association between the MEF2A gene and myocardial infarction. Circulation. 117:185–191. 2008. View Article : Google Scholar
4	Wang Q: Advances in the genetic basis of coronary artery disease. Curr Atheroscler Rep. 7:235–241. 2005. View Article : Google Scholar : PubMed/NCBI
5	Han Y, Yang Y, Zhang X, Yan C, Xi S and Kang J: Relationship of the CAG repeat polymorphism of the MEF2A gene and coronary artery disease in a Chinese population. Clin Chem Lab Med. 45:987–992. 2007. View Article : Google Scholar : PubMed/NCBI
6	Mayer B, Erdmann J and Schunkert H: Genetics and heritability of coronary artery disease and myocardial infarction. Clin Res Cardiol. 96:1–7. 2007. View Article : Google Scholar
7	Topol EJ, Smith J, Plow EF and Wang QK: Genetic susceptibility to myocardial infarction and coronary artery disease. Hum Mol Genet. 15:R117–R123. 2006. View Article : Google Scholar : PubMed/NCBI
8	Incalcaterra E, Hoffmann E, Averna MR and Caimi G: Genetic risk factors in myocardial infarction at young age. Minerva Cardioangiol. 52:287–312. 2004.PubMed/NCBI
9	Broeckel U, Hengstenberg C, Mayer B, Holmer S, Martin LJ, Comuzzie AG, Blangero J, Nürnberg P, Reis A, Riegger GA, et al: A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet. 30:210–214. 2002. View Article : Google Scholar : PubMed/NCBI
10	Ikewaki K, Matsunaga A, Han H, Watanabe H, Endo A, Tohyama J, Kuno M, Mogi J, Sugimoto K, Tada N, et al: A novel two nucleotide deletion in the apolipoprotein A-I gene, apoA-I Shinbashi, associated with high density lipoprotein deficiency, corneal opacities, planar xanthomas, and premature coronary artery disease. Atherosclerosis. 172:39–45. 2004. View Article : Google Scholar : PubMed/NCBI
11	Weng L, Kavaslar N, Ustaszewska A, Doelle H, Schackwitz W, Hébert S, Cohen JC, McPherson R and Pennacchio LA: Lack of MEF2A mutations in coronary artery disease. J Clin Invest. 115:1016–1020. 2005. View Article : Google Scholar : PubMed/NCBI
12	Altshuler D and Hirschhorn JN: MEF2A sequence variants and coronary artery disease: A change of heart? J Clin Invest. 115:831–833. 2005. View Article : Google Scholar : PubMed/NCBI
13	Bhagavatula MR, Fan C, Shen GQ, Cassano J, Plow EF, Topol EJ and Wang Q: Transcription factor MEF2A mutations in patients with coronary artery disease. Hum Mol Genet. 13:3181–3188. 2004. View Article : Google Scholar : PubMed/NCBI
14	World Health Organization: Nomenclature and criteria for diagnosis of ischemic heart disease: Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation. 59:607–609. 1979. View Article : Google Scholar
15	Guo Y, Yuan L, Yi J, Xiao J, Xu H, Lv H, Xiong W, Zheng W, Guan L, Zhang J, et al: Identification of a GJA3 mutation in a Chinese family with congenital nuclear cataract using exome sequencing. Indian. J Biochem Biophys. 50:253–258. 2013.
16	Wang JL, Cao L, Li XH, Hu ZM, Li JD, Zhang JG, Liang Y, San A, Li N, Chen SQ, et al: Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias. Brain. 134:3493–3501. 2011. View Article : Google Scholar : PubMed/NCBI
17	Shi Y, Li Y, Zhang D, Zhang H, Li Y, Lu F, Liu X, He F, Gong B, Cai L, et al: Exome sequencing identifies ZNF644 mutations in high myopia. PLoS Genet. 7:e10020842011. View Article : Google Scholar : PubMed/NCBI
18	Yuan L, Song Z, Xu H, Gu S, Zhu A, Gong L, Zhao Y and Deng H: EIF4G1 Ala502Val and Arg1205His variants in Chinese patients with Parkinson disease. Neurosci Lett. 543:69–71. 2013. View Article : Google Scholar : PubMed/NCBI
19	Yuan L, Wu S, Xu H, Xiao J, Yang Z, Xia H, Liu A, Hu P, Lu A, Chen Y, et al: Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing. Biol Chem. 396:27–33. 2015. View Article : Google Scholar