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

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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 . https://doi.org/10.1186/s12881-018-0574-0

Title: Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients
Author: 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
Other contributor: University of Helsinki, Department of Medicine
University of Helsinki, Complex Disease Genetics
University of Helsinki, Clinicum
University of Helsinki, Kimmo Kontula / Principal Investigator
University of Helsinki, Clinicum
University of Helsinki, Department of Medicine
University of Helsinki, HUS Heart and Lung Center
University of Helsinki, Clinicum







Date: 2018-04-05
Language: eng
Number of pages: 10
Belongs to series: BMC Medical Genetics
ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-018-0574-0
URI: http://hdl.handle.net/10138/235203
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.
Subject: Long QT syndrome
Cardiac arrhythmia
Risk stratification
beta-blocker
Implantable cardioverter-defibrillator
IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR
MUTATION-SPECIFIC RISK
CARDIAC EVENTS
BETA-BLOCKERS
STRATIFICATION
GENOTYPE
MANAGEMENT
IDENTIFICATION
ARRHYTHMIAS
EFFICACY
3111 Biomedicine
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