CLINICAL RESEARCH: ELECTROPHYSIOLOGIC DISORDERS
Modulating effects of age and gender on the clinical course of long QT syndrome by genotype
Wojciech Zareba, MD, PhD, FACC*,*,
Arthur J. Moss, MD, FACC*,
Emanuela H. Locati, MD, PhD ,
Michael H. Lehmann, MD, FACC ,
Derick R. Peterson, PhD ,
W. Jackson Hall, PhD,
Peter J. Schwartz, MD, FACC||,
G. Michael Vincent, MD, FACC¶,
Silvia G. Priori, MD, PhD#,
Jesaia Benhorin, MD, FACC**,
Jeffrey A. Towbin, MD, FACC,
Jennifer L. Robinson, MS*,
Mark L. Andrews, BBA*,
Carlo Napolitano, MD#,
Katherine Timothy¶,
Li Zhang, MD¶,
Aharon Medina, MD** International Long QT Syndrome Registry
* Department of MedicineRochester, New York, USA
Department of Biostatistics, University of Rochester School of Medicine, Rochester, New York, USA
Department of Cardiology, University of Perugia, Perugia, Italy
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
|| Department of Cardiology, University of Pavia, and Policlinico San Matteo, IRCCS, Pavia, Italy
¶ LDS Hospital, Salt Lake City, Utah, USA
# Molecular Cardiology, IRCCS, Fondazione S. Maugeri, Pavia, Italy
** Bikur Cholim Hospital, University of Jerusalem, Jerusalem, Israel
Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas, USA
Manuscript received December 30, 2002;
revised manuscript received March 19, 2003,
accepted April 10, 2003.
* Reprint requests and correspondence: Dr. Wojciech Zareba, Heart Research Follow-up Program, Box 653, University of Rochester Medical Center, Rochester, New York 14642-8653, USA.
heartwz{at}heart.rochester.edu
OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration.
BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited.
METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children  15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype.
RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both).
CONCLUSIONS: Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.
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Abbreviations and Acronyms
| | HR | | hazard ratio | | IKr | | HERG potassium channel | | IKs | | KCNQ1 potassium channel | | INa | | SCN5A sodium channel | | LQTS | | long QT syndrome | | LQT1 | | long QT syndrome caused by the KCNQ1 potassium channel gene mutations | | LQT2 | | long QT syndrome caused by the HERG potassium channel gene mutations | | LQT3 | | long QT syndrome caused by the SCN5A sodium channel gene mutation |
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