Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients

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Standard

Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients. / Jons, Christian; O-Uchi, Jin; Moss, Arthur J; Reumann, Matthias; Rice, John J; Goldenberg, Ilan; Zareba, Wojciech; Wilde, Arthur A M; Shimizu, Wataru; Kanters, Jørgen K.; McNitt, Scott; Hofman, Nynke; Robinson, Jennifer L; Lopes, Coeli M B.

I: Science Translational Medicine, Bind 3, Nr. 76, 30.03.2011, s. 76ra28.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Jons, C, O-Uchi, J, Moss, AJ, Reumann, M, Rice, JJ, Goldenberg, I, Zareba, W, Wilde, AAM, Shimizu, W, Kanters, JK, McNitt, S, Hofman, N, Robinson, JL & Lopes, CMB 2011, 'Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients', Science Translational Medicine, bind 3, nr. 76, s. 76ra28. https://doi.org/10.1126/scitranslmed.3001551

APA

Jons, C., O-Uchi, J., Moss, A. J., Reumann, M., Rice, J. J., Goldenberg, I., Zareba, W., Wilde, A. A. M., Shimizu, W., Kanters, J. K., McNitt, S., Hofman, N., Robinson, J. L., & Lopes, C. M. B. (2011). Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients. Science Translational Medicine, 3(76), 76ra28. https://doi.org/10.1126/scitranslmed.3001551

Vancouver

Jons C, O-Uchi J, Moss AJ, Reumann M, Rice JJ, Goldenberg I o.a. Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients. Science Translational Medicine. 2011 mar. 30;3(76):76ra28. https://doi.org/10.1126/scitranslmed.3001551

Author

Jons, Christian ; O-Uchi, Jin ; Moss, Arthur J ; Reumann, Matthias ; Rice, John J ; Goldenberg, Ilan ; Zareba, Wojciech ; Wilde, Arthur A M ; Shimizu, Wataru ; Kanters, Jørgen K. ; McNitt, Scott ; Hofman, Nynke ; Robinson, Jennifer L ; Lopes, Coeli M B. / Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients. I: Science Translational Medicine. 2011 ; Bind 3, Nr. 76. s. 76ra28.

Bibtex

@article{5a7c859123a94775bef1e5eb019e7479,
title = "Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients",
abstract = "Inherited long QT syndrome (LQTS) is caused by mutations in ion channels that delay cardiac repolarization, increasing the risk of sudden death from ventricular arrhythmias. Currently, the risk of sudden death in individuals with LQTS is estimated from clinical parameters such as age, gender, and the QT interval, measured from the electrocardiogram. Even though a number of different mutations can cause LQTS, mutation-specific information is rarely used clinically. LQTS type 1 (LQT1), one of the most common forms of LQTS, is caused by mutations in the slow potassium current (I(Ks)) channel a subunit KCNQ1. We investigated whether mutation-specific changes in I(Ks) function can predict cardiac risk in LQT1. By correlating the clinical phenotype of 387 LQT1 patients with the cellular electrophysiological characteristics caused by an array of mutations in KCNQ1, we found that channels with a decreased rate of current activation are associated with increased risk of cardiac events (hazard ratio=2.02), independent of the clinical parameters usually used for risk stratification. In patients with moderate QT prolongation (a QT interval less than 500 ms), slower activation was an independent predictor for cardiac events (syncope, aborted cardiac arrest, and sudden death) (hazard ratio = 2.10), whereas the length of the QT interval itself was not. Our results indicate that genotype and biophysical phenotype analysis may be useful for risk stratification of LQT1 patients and suggest that slow channel activation is associated with an increased risk of cardiac events.",
keywords = "Adolescent, Adult, Animals, Child, Child, Preschool, Computer Simulation, Electrophysiology, Genetic Predisposition to Disease, Genotype, Humans, Infant, Ion Channel Gating, KCNQ1 Potassium Channel, Kaplan-Meier Estimate, Long QT Syndrome, Male, Models, Biological, Mutation, Oocytes, Phenotype, Proportional Hazards Models, Registries, Risk Factors, Xenopus laevis, Young Adult",
author = "Christian Jons and Jin O-Uchi and Moss, {Arthur J} and Matthias Reumann and Rice, {John J} and Ilan Goldenberg and Wojciech Zareba and Wilde, {Arthur A M} and Wataru Shimizu and Kanters, {J{\o}rgen K.} and Scott McNitt and Nynke Hofman and Robinson, {Jennifer L} and Lopes, {Coeli M B}",
year = "2011",
month = mar,
day = "30",
doi = "10.1126/scitranslmed.3001551",
language = "English",
volume = "3",
pages = "76ra28",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "american association for the advancement of science",
number = "76",

}

RIS

TY - JOUR

T1 - Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients

AU - Jons, Christian

AU - O-Uchi, Jin

AU - Moss, Arthur J

AU - Reumann, Matthias

AU - Rice, John J

AU - Goldenberg, Ilan

AU - Zareba, Wojciech

AU - Wilde, Arthur A M

AU - Shimizu, Wataru

AU - Kanters, Jørgen K.

AU - McNitt, Scott

AU - Hofman, Nynke

AU - Robinson, Jennifer L

AU - Lopes, Coeli M B

PY - 2011/3/30

Y1 - 2011/3/30

N2 - Inherited long QT syndrome (LQTS) is caused by mutations in ion channels that delay cardiac repolarization, increasing the risk of sudden death from ventricular arrhythmias. Currently, the risk of sudden death in individuals with LQTS is estimated from clinical parameters such as age, gender, and the QT interval, measured from the electrocardiogram. Even though a number of different mutations can cause LQTS, mutation-specific information is rarely used clinically. LQTS type 1 (LQT1), one of the most common forms of LQTS, is caused by mutations in the slow potassium current (I(Ks)) channel a subunit KCNQ1. We investigated whether mutation-specific changes in I(Ks) function can predict cardiac risk in LQT1. By correlating the clinical phenotype of 387 LQT1 patients with the cellular electrophysiological characteristics caused by an array of mutations in KCNQ1, we found that channels with a decreased rate of current activation are associated with increased risk of cardiac events (hazard ratio=2.02), independent of the clinical parameters usually used for risk stratification. In patients with moderate QT prolongation (a QT interval less than 500 ms), slower activation was an independent predictor for cardiac events (syncope, aborted cardiac arrest, and sudden death) (hazard ratio = 2.10), whereas the length of the QT interval itself was not. Our results indicate that genotype and biophysical phenotype analysis may be useful for risk stratification of LQT1 patients and suggest that slow channel activation is associated with an increased risk of cardiac events.

AB - Inherited long QT syndrome (LQTS) is caused by mutations in ion channels that delay cardiac repolarization, increasing the risk of sudden death from ventricular arrhythmias. Currently, the risk of sudden death in individuals with LQTS is estimated from clinical parameters such as age, gender, and the QT interval, measured from the electrocardiogram. Even though a number of different mutations can cause LQTS, mutation-specific information is rarely used clinically. LQTS type 1 (LQT1), one of the most common forms of LQTS, is caused by mutations in the slow potassium current (I(Ks)) channel a subunit KCNQ1. We investigated whether mutation-specific changes in I(Ks) function can predict cardiac risk in LQT1. By correlating the clinical phenotype of 387 LQT1 patients with the cellular electrophysiological characteristics caused by an array of mutations in KCNQ1, we found that channels with a decreased rate of current activation are associated with increased risk of cardiac events (hazard ratio=2.02), independent of the clinical parameters usually used for risk stratification. In patients with moderate QT prolongation (a QT interval less than 500 ms), slower activation was an independent predictor for cardiac events (syncope, aborted cardiac arrest, and sudden death) (hazard ratio = 2.10), whereas the length of the QT interval itself was not. Our results indicate that genotype and biophysical phenotype analysis may be useful for risk stratification of LQT1 patients and suggest that slow channel activation is associated with an increased risk of cardiac events.

KW - Adolescent

KW - Adult

KW - Animals

KW - Child

KW - Child, Preschool

KW - Computer Simulation

KW - Electrophysiology

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Infant

KW - Ion Channel Gating

KW - KCNQ1 Potassium Channel

KW - Kaplan-Meier Estimate

KW - Long QT Syndrome

KW - Male

KW - Models, Biological

KW - Mutation

KW - Oocytes

KW - Phenotype

KW - Proportional Hazards Models

KW - Registries

KW - Risk Factors

KW - Xenopus laevis

KW - Young Adult

U2 - 10.1126/scitranslmed.3001551

DO - 10.1126/scitranslmed.3001551

M3 - Journal article

C2 - 21451124

VL - 3

SP - 76ra28

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 76

ER -

ID: 33910765