Genetic association analyses highlight biological pathways underlying mitral valve prolapse
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Author
Dina, Christian
Bouatia-Naji, Nabila
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
Su Hao, LO
Dolmatova, Elena
Simonet, Floriane
Lecointe, Simon
Kyndt, Florence
Redon, Richard
Le Marec, Hervé
Froguel, Philippe
Vasan, Ramachandran S.
Bruneval, Patrick
Norris, Russell A.
Schott, Jean-Jacques
Hagege, Albert A.
Jeunemaitre, Xavier
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.3383Metadata
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Dina, C., N. Bouatia-Naji, N. Tucker, F. N. Delling, K. Toomer, R. Durst, M. Perrocheau, et al. 2016. “Genetic association analyses highlight biological pathways underlying mitral valve prolapse.” Nature genetics 47 (10): 1206-1211. doi:10.1038/ng.3383. http://dx.doi.org/10.1038/ng.3383.Abstract
Non-syndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown aetiology that predisposes to mitral regurgitation, heart failure and sudden death1. Previous family and pathophysiological studies suggest a complex pattern of inheritance2–5. We performed a meta-analysis of two genome-wide association studies in 1,442 cases and 2,439 controls. We identified and replicated in 1,422 cases and 6,779 controls six loci and provide functional evidence for candidate genes. We highlight LMCD1 encoding a transcription factor6, for which morpholino knockdown in zebrafish results in atrioventricular (AV) valve regurgitation. A similar zebrafish phenotype was obtained for tensin1 (TNS1), a focal adhesion protein involved in cytoskeleton organization. We also show the expression of tensin1 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 repair7.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773907/pdf/Terms of Use
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