{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:24:42Z","timestamp":1760243082115,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,7,10]],"date-time":"2015-07-10T00:00:00Z","timestamp":1436486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>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 (MMP2) known to regulate the ECM turnover by direct degradation of proteins and for which transgenic mice develop MVP. Direct sequencing of exons of MMP2 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 MMP2 locus. The association study in two case controls sets (NCases = 1073 and NControls = 1635) provided suggestive evidence for the association of rs1556888 located downstream MMP2 with the risk of MVP, especially in patients with the fibroelastic defiency form. Our study does not support the contribution of MMP2 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.<\/jats:p>","DOI":"10.3390\/jcdd2030176","type":"journal-article","created":{"date-parts":[[2015,7,13]],"date-time":"2015-07-13T03:49:22Z","timestamp":1436759362000},"page":"176-189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigation of the Matrix Metalloproteinase-2 Gene in Patients with Non-Syndromic Mitral Valve Prolapse"],"prefix":"10.3390","volume":"2","author":[{"given":"Ma\u00eblle","family":"Perrocheau","sequence":"first","affiliation":[{"name":"Paris Cardiovascular Research Center, INSERM UMR970, 56 rue Leblanc, Paris F-75015, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, 12 rue de l'\u00e9cole de medicine,  Paris F-75006, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soto","family":"Kiando","sequence":"additional","affiliation":[{"name":"Paris Cardiovascular Research Center, INSERM UMR970, 56 rue Leblanc, Paris F-75015, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, 12 rue de l'\u00e9cole de medicine,  Paris F-75006, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00e9wi","family":"Vernerey","sequence":"additional","affiliation":[{"name":"Paris Cardiovascular Research Center, INSERM UMR970, 56 rue Leblanc, Paris F-75015, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, 12 rue de l'\u00e9cole de medicine,  Paris F-75006, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Dina","sequence":"additional","affiliation":[{"name":"INSERM UMR1087, CNRS UMR 6291, Institut du Thorax, 8 Quai Moncousu, Nantes F-44007, France"},{"name":"Centre Hospitalier Universitaire (CHU) Nantes, Universit\u00e9 de Nantes, 8 Quai Moncousu,  Nantes F-44007, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Galan","sequence":"additional","affiliation":[{"name":"Equipe de Recherche en Epid\u00e9miologie Nutritionnelle (EREN), Centre d'Epid\u00e9miologie et Statistiques Sorbonne Paris Cit\u00e9, Inserm (U1153), Inra (U1125), Cnam, Universit\u00e9 Paris 13, COMUE Sorbonne Paris Cit\u00e9, Bobigny F-93017, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Hagege","sequence":"additional","affiliation":[{"name":"Paris Cardiovascular Research Center, INSERM UMR970, 56 rue Leblanc, Paris F-75015, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, 12 rue de l'\u00e9cole de medicine,  Paris F-75006, France"},{"name":"Department of Cardiology, H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance publique-H\u00f4pitaux de Paris (AP-HP), 20 rue Leblanc, Paris F-75015, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Jeunemaitre","sequence":"additional","affiliation":[{"name":"Paris Cardiovascular Research Center, INSERM UMR970, 56 rue Leblanc, Paris F-75015, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, 12 rue de l'\u00e9cole de medicine,  Paris F-75006, France"},{"name":"Department of genetics, H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance publique-H\u00f4pitaux de Paris (AP-HP), 20 rue Leblanc, Paris F-75015, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabila","family":"Bouatia-Naji","sequence":"additional","affiliation":[{"name":"Paris Cardiovascular Research Center, INSERM UMR970, 56 rue Leblanc, Paris F-75015, France"},{"name":"Paris Descartes University, Sorbonne Paris Cit\u00e9, 12 rue de l'\u00e9cole de medicine,  Paris F-75006, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1161\/01.CIR.0000028933.34260.09","article-title":"Natural history of asymptomatic mitral valve prolapse in the community","volume":"106","author":"Avierinos","year":"2002","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0140-6736(05)17869-6","article-title":"Mitral valve prolapse","volume":"365","author":"Hayek","year":"2005","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0735-1097(99)00464-7","article-title":"Echocardiographic predictors of left ventricular outflow tract obstruction and systolic anterior motion of the mitral valve after mitral valve reconstruction for myxomatous valve disease","volume":"34","author":"Maslow","year":"1999","journal-title":"J. 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