| Title: |
Genetic association analyses highlight biological pathways underlying mitral valve prolapse |
| Authors: |
Dina, Christian; Bouatia-Naji, Nabila; Tucker, Nathan; Delling, Francesca N.; Toomer, Katelynn; Durst, Ronen; Perrocheau, Maelle; Fernandez-Friera, Leticia; Solis, Jorge; Le Tourneau, Thierry; Chen, Ming-Huei; Probst, Vincent; Bosse, Yohan; Pibarot, Philippe; Zelenika, Diana; Lathrop, Mark; Hercberg, Serge; Roussel, Ronan; Benjamin, Emelia J.; Bonnet, Fabrice; Lo, Su Hao; Dolmatova, Elena; Lecointe, Simon; Kyndt, Florence; Redon, Richard; Le Marec, Hervé; Froguel, Philippe; Ellinor, Patrick T.; Vasan, Ramachandran S.; Bruneval, Patrick; Markwald, Roger R.; Norris, Russell A.; Milan, David J.; Slaugenhaupt, Susan A.; Levine, Robert A.; Schott, Jean-Jacques; Hagege, Albert A.; Jeunemaitre, Xavier |
| Contributors: |
ITX - unité de recherche de l'institut du thorax (ITX); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970); Hôpital Européen Georges Pompidou APHP (HEGP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM); Institut de cardiologie de Québec; Université Laval Québec (ULaval)-Centre Hospitalier de Laval (CH Laval); Centre National de Génotypage (CNG); Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Hôpital Avicenne AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)); Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM); Centre de Recherche des Cordeliers (CRC (UMR_S 872)); Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Foie, métabolismes et cancer; Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS); Imperial College London; Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO); Université Paris Descartes - Paris 5 (UPD5); Nantes Hospital (CHU Nantes); US National Institutes of Health (NIH) K24 HL67434 R01 HL72265 HL109506; French young investigator fund ANR-13-ISV1-0006-0; Hassenfeld Scholar Program; NIH HL092577 HL104156 K24HL105780 HL065962; American Heart Association 13EIA14220013 15GRNT25080052; Fondation Leducq 14CVD01; Canadian Institutes of Health Research (CIHR) MOP-102737 MOP-114997 MOP-126072; Fonds de recherche Quebec-Sante (FRQS); CIHR MOP-102481 MOP-137058; Spanish Society of Cardiology; fund for medical discovery of the Massachusetts General Hospital; European Commission; US National Institutes of Health C06 RR018823; Extramural Research Facilities Program of the Heart, Lung, and Blood Institute R01-HL33756 COBRE 1P30 GM103342 8P20 GM103444-07 R01-HL127692; INSERM; French Society of Cardiology; ANR-13-ISV1-0006,Gea,GEnetic and mechanistic studies of primary Aldosteronism(2013) |
| Source: |
ISSN: 1061-4036. |
| Publisher Information: |
HAL CCSD; Nature Publishing Group |
| Publication Year: |
2015 |
| Collection: |
Université de Rennes 1: Publications scientifiques (HAL) |
| Subject Terms: |
GENOME-WIDE ASSOCIATION; CARDIAC VALVULAR DYSTROPHY; NATURAL-HISTORY; PATHOGENESIS; METAANALYSIS; FILAMIN-A; MARFAN-SYNDROME; CELL-MIGRATION; EXPRESSION; LOCUS; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system |
| Description: |
International audience ; Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart failure and sudden death. Previous family and pathophysiological studies suggest a complex pattern of inheritance. We performed a meta-analysis of 2 genome-wide association studies in 1,412 MVP cases and 2,439 controls. We identified 6 loci, which we replicated in 1,422 cases and 6,779 controls, and provide functional evidence for candidate genes. We highlight LMCD1 (LIM and cysteine-rich domains 1), which encodes a transcription factor and for which morpholino knockdown of the ortholog in zebrafish resulted in atrioventricular valve regurgitation. A similar zebrafish phenotype was obtained with knockdown of the ortholog of TNS1, which encodes tensin 1, a focal adhesion protein involved in cytoskeleton organization. We also showed expression of tensin 1 during valve morphogenesis and describe enlarged posterior mitral leaflets in Tns1(-/-) mice. This study identifies the first risk loci for MVP and suggests new mechanisms involved in mitral valve regurgitation, the most common indication for mitral valve repair |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISBN: |
978-0-00-361969-0; 0-00-361969-9 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/26301497; PRODINRA: 336437; PUBMED: 26301497; WOS: 000361969900017 |
| DOI: |
10.1038/ng.3383 |
| Availability: |
https://univ-rennes.hal.science/hal-01191656; https://univ-rennes.hal.science/hal-01191656v1/document; https://univ-rennes.hal.science/hal-01191656v1/file/nihms711882.pdf; https://doi.org/10.1038/ng.3383 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.7EAE4C98 |
| Database: |
BASE |