Clinical research: electrophysiologic disorders
Modulating effects of age and gender on the clinical course of long QT syndrome by genotype

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Abstract

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.

Abbreviations

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

Cited by (0)

Supported, in part, by research grants HL-33843 and HL-51618 from the National Institutes of Health.