Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients

Show simple item record Koponen, Mikael Havulinna, Aki S. Marjamaa, Annukka Tuiskula, Annukka M. Salomaa, Veikko Laitinen-Forsblom, Päivi J. Piippo, Kirsi Toivonen, Lauri Kontula, Kimmo Viitasalo, Matti Swan, Heikki 2018-05-17T08:25:01Z 2018-05-17T08:25:01Z 2018-04-05
dc.identifier.citation Koponen , M , Havulinna , A S , Marjamaa , A , Tuiskula , A M , Salomaa , V , Laitinen-Forsblom , P J , Piippo , K , Toivonen , L , Kontula , K , Viitasalo , M & Swan , H 2018 , ' Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients ' , BMC Medical Genetics , vol. 19 , 56 .
dc.identifier.other PURE: 106955599
dc.identifier.other PURE UUID: 48867cbc-66a9-4471-8366-7bb50ed25ecf
dc.identifier.other WOS: 000429568100002
dc.identifier.other Scopus: 85045010647
dc.description.abstract Background: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving beta-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. Methods: A follow-up study covering a mean of 18.6 +/- 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18-40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events. Results: In mutation carriers, risk factors for cardiac events before initiation of beta-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p <0.001), a cardiac event before the age of 18 years (HR = 5.9, p <0.001), and QTc >= 500 ms (vs <470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0-3.9, p <0.001-0.03) compared to G589D, c. 1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c. 453delC, L552S and R176W mutations associated with lower risk (HR = 0.11-0.23, p <0.001) than other KCNH2 mutations. Conclusions: LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof BMC Medical Genetics
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Long QT syndrome
dc.subject Cardiac arrhythmia
dc.subject Risk stratification
dc.subject beta-blocker
dc.subject Implantable cardioverter-defibrillator
dc.subject BETA-BLOCKERS
dc.subject GENOTYPE
dc.subject MANAGEMENT
dc.subject ARRHYTHMIAS
dc.subject EFFICACY
dc.subject 3111 Biomedicine
dc.title Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients en
dc.type Article
dc.contributor.organization Department of Medicine
dc.contributor.organization HUS Heart and Lung Center
dc.contributor.organization Complex Disease Genetics
dc.contributor.organization Clinicum
dc.contributor.organization Kimmo Kontula Research Group
dc.contributor.organization University of Helsinki
dc.contributor.organization Kardiologian yksikkö
dc.contributor.organization HUS Internal Medicine and Rehabilitation
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1471-2350
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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