Cel Cardiovascular disease is a leading cause of death worldwide. A number of these deaths are due to severe disturbances in cardiac rhythm (ventricular tachycardia or fibrillation) that lead to a fatal cardiac arrhythmia or sudden cardiac death. Ventricular tachycardia or fibrillation can occur during exercise or excitement, and has been associated with an underlying disorder called Long QT Syndrome (LQTS). The clinical course of LQTS is variable, some patients remain asymptomatic while others develop ventricular tachycardia or fibrillation, resulting in sudden death. LQTS is characterised by an abnormally long heart-beat length (QT interval) by ECG. The QT interval corrected for heart rate (QTc) is variable in the general population and has been shown to be highly predictive of a person’s risk of ventricular tachycardia or fibrillation and sudden cardiac death. ~75% of all LQTS cases have mutations in genes regulating QTc. However, there is large variation in the penetrance of these mutations on QTc, even within single affected families. Recent studies have shown that common genetic variants (SNPs) in genes coding for ionic channels, or neuronal nitric oxide synthase 1 regulator, NOS1AP, can affect QTc in the normal healthy population. Therefore SNPs within LQTS loci may modulate the effect of known mutations in LQTS patients. We will study SNPs in a large cohort of LQTS families with known mutations and predict that SNPs which prolong QTc are associated with a higher risk of cardiac events in the probands compared to asymptomatic LQTS patients. We will confirm the link between QTc and cardiac events in a large population, and that genotype is a determining factor for the age of occurrence of the first cardiac event. This research will help to explain the partial penetrance and high variability of QTc and risk of sudden death in LQTS families, and will have important implications for the early identification and prevention of arrhythmias and sudden cardiac death. Dziedzina nauki medical and health sciencesclinical medicinecardiologycardiovascular diseasescardiac arrhythmianatural sciencesbiological sciencesgeneticsmutation Słowa kluczowe Cardiology Cell biology Medical genetics Molecular biology Molecular genetics Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) PEOPLE-2007-4-2.IIF - Marie Curie Action: "International Incoming Fellowships" Zaproszenie do składania wniosków FP7-PEOPLE-2007-4-2-IIF Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IIF - International Incoming Fellowships (IIF) Koordynator INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Wkład UE € 164 777,73 Adres RUE DE TOLBIAC 101 75654 Paris Francja Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Kontakt administracyjny Pascale Guicheney (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
