Investigation of the Matrix Metalloproteinase-2 Gene in Patients with Non-Syndromic Mitral Valve Prolapse.
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Date publication
juillet 2015
Journal
Journal of cardiovascular development and disease
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VERNEREY Dewi
Tous les auteurs :
Perrocheau M, Kiando SR, Vernerey D, Dina C, Galan P, Hagege A, Jeunemaitre X, Bouatia-Naji N
Lien Pubmed
Résumé
Non-syndromic mitral valve prolapse (MVP) is a common degenerative valvulopathy, predisposing to arrhythmia and sudden death. The etiology of MVP is suspected to be under genetic control, as supported by familial cases and its manifestation in genetic syndrome (e.g., Marfan syndrome). One candidate etiological mechanism is a perturbation of the extracellular matrix (ECM) remodeling of the valve. To test this hypothesis, we assessed the role of genetic variants in the matrix metalloproteinase 2 gene () known to regulate the ECM turnover by direct degradation of proteins and for which transgenic mice develop MVP. Direct sequencing of exons of in 47 unrelated patients and segregation analyses in families did not reveal any causative mutation. We studied eight common single nucleotide polymorphisms (TagSNPs), which summarize the genetic information at the locus. The association study in two case controls sets (N = 1073 and N = 1635) provided suggestive evidence for the association of rs1556888 located downstream with the risk of MVP, especially in patients with the fibroelastic defiency form. Our study does not support the contribution of rare variation in the etiology to MVP in humans, though further genetic and molecular investigation is required to confirm our current suggestive association of one common variant.
Référence
J Cardiovasc Dev Dis. 2015 Jul 10;2(3):176-189