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Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect

  • Authors:
    • Fadi Liu
    • Xiao Liu
    • Zhenyan Xu
    • Ping Yuan
    • Qiongqiong Zhou
    • Jiejing Jin
    • Xia Yan
    • Zixuan Xu
    • Qing Cao
    • Jianhua Yu
    • Yingzhang Cheng
    • Rong Wan
    • Kui Hong
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1527-1536
    |
    Published online on: November 15, 2017
       https://doi.org/10.3892/mmr.2017.8088
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Abstract

The Ellis-van Creveld (EVC) gene is associated with various congenital heart diseases. However, studies on EVC gene variations in ventricular septal defect (VSD) and the underlying molecular mechanisms are sparse. The present study detected 11 single‑nucleotide polymorphisms (SNPs) in 65 patients with VSD and 210 control patients from the Chinese Han population. Of the identified SNPs only the c.1727G>A SNP site was positively associated with the development of VSD (P<0.007). A known mutation, c.343C>G, was also identified, which causes a leucine to valine substitution at amino acid 115 of the EVC protein (p.L115V). The results of functional prediction indicated that c.343C>G may be a pathogenic mutation. In addition, in NIH3T3 mouse embryonic fibroblast cells, the EVC c.343C>G mutation significantly decreased cell proliferation and increased apoptosis. Further investigation demonstrated that in NIH3T3 cells, overexpression of EVC c.343C>G mutation reduced the binding between EVC and smoothened, which further downregulated the activity of the hedgehog (Hh) signaling pathway and the expression of downstream cyclin D1 and B‑cell lymphoma 2 proteins with SAG. The c.1727G>A SNP of the EVC gene increased VSD susceptibility in patients from the Chinese Han population. The molecular mechanism underlying the development of VSD induced by the EVC c.343C>G mutation may be due to a reduction in the anti‑apoptotic and proliferative abilities of cardiomyocytes via downregulation of Hh pathway activity. The results of the present study may provide novel targets for the diagnosis and treatment of patients with VSD.
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Copy and paste a formatted citation
Spandidos Publications style
Liu F, Liu X, Xu Z, Yuan P, Zhou Q, Jin J, Yan X, Xu Z, Cao Q, Yu J, Yu J, et al: Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect. Mol Med Rep 17: 1527-1536, 2018.
APA
Liu, F., Liu, X., Xu, Z., Yuan, P., Zhou, Q., Jin, J. ... Hong, K. (2018). Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect. Molecular Medicine Reports, 17, 1527-1536. https://doi.org/10.3892/mmr.2017.8088
MLA
Liu, F., Liu, X., Xu, Z., Yuan, P., Zhou, Q., Jin, J., Yan, X., Xu, Z., Cao, Q., Yu, J., Cheng, Y., Wan, R., Hong, K."Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect". Molecular Medicine Reports 17.1 (2018): 1527-1536.
Chicago
Liu, F., Liu, X., Xu, Z., Yuan, P., Zhou, Q., Jin, J., Yan, X., Xu, Z., Cao, Q., Yu, J., Cheng, Y., Wan, R., Hong, K."Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect". Molecular Medicine Reports 17, no. 1 (2018): 1527-1536. https://doi.org/10.3892/mmr.2017.8088
Copy and paste a formatted citation
x
Spandidos Publications style
Liu F, Liu X, Xu Z, Yuan P, Zhou Q, Jin J, Yan X, Xu Z, Cao Q, Yu J, Yu J, et al: Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect. Mol Med Rep 17: 1527-1536, 2018.
APA
Liu, F., Liu, X., Xu, Z., Yuan, P., Zhou, Q., Jin, J. ... Hong, K. (2018). Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect. Molecular Medicine Reports, 17, 1527-1536. https://doi.org/10.3892/mmr.2017.8088
MLA
Liu, F., Liu, X., Xu, Z., Yuan, P., Zhou, Q., Jin, J., Yan, X., Xu, Z., Cao, Q., Yu, J., Cheng, Y., Wan, R., Hong, K."Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect". Molecular Medicine Reports 17.1 (2018): 1527-1536.
Chicago
Liu, F., Liu, X., Xu, Z., Yuan, P., Zhou, Q., Jin, J., Yan, X., Xu, Z., Cao, Q., Yu, J., Cheng, Y., Wan, R., Hong, K."Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect". Molecular Medicine Reports 17, no. 1 (2018): 1527-1536. https://doi.org/10.3892/mmr.2017.8088
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