I-CARE project - Jean-Jacques Schott
Jean-Jacques Schott is the scientific leader of this ANR-funded project dedicated to unravel the genetic basis of mitral valve prolapse.
Abstract
Mitral valve prolapse (MVP) is a common cardiac valve disease. Recent findings from our team have highlighted a strong genetic component for MVP reinforcing the concept that valve degeneration is not solely related to aging and opens new fields of investigation in cardiac valve disease. There is strong evidence for high genetic heterogeneity in mitral valve disease. Better characterizing the complex interplay between rare and common genetic variant will help in further understanding the pathophysiology of this valve disorder.
In this project, we aim to establish a new collaborative translational research program as a follow up of a previous Transatlantic Leducq Network focused on mitral valve disease. More specifically we plan to further investigate the genetic basis of valve degeneration through an integrated research program combining high-throughput genetic screening and functional investigations. We will develop two complementary approaches:
1. Genetic investigations to further address the heart valve biology
- Identify new MVP-susceptibility genes and estimate their relative roles in the burden of severe clinical forms of MVP.
- Pursue the GWAS-based investigation to identify additional loci to better understand the contribution of common genetic variants in MVP risk. More specifically, we will investigate the molecular mechanisms underlying the most interesting association signal and best candidate gene in the TNS locus and follow-up our discovery efforts by investigating more deeply existing and upcoming GWAS meta-analyses with promising association signals.
- Early biomarkers for this severe degenerative disease
- New clinical / echocardiographic criteria to identify patients at risk, in conjunction or independently of the genetic background, and prevent MVP complications. This project will be accomplished by applying state-of-the-art methods of molecular genetics, bioinformatics, cell biology and advanced MVP imaging.
