Key result
KCNH2 pore site mutations were associated with a significantly younger age at first cardiac event compared to non-pore mutations, with the higher arrhythmic risk driven primarily by non-probands.
Why the study?
Does the location of KCNH2 mutations in the pore region increase the risk of cardiac events in Japanese LQT2 patients compared to non-pore mutations?
Cohort (n=118)
Yes
Does the location of KCNH2 mutations in the pore region increase the risk of cardiac events in Japanese LQT2 patients compared to non-pore mutations?
In Japanese LQT2 patients, family members (non-probands) with KCNH2 pore site mutations are at a significantly higher risk of early cardiac events compared to those with non-pore mutations.
May not yet alter LQT2 risk stratification; extends genotype-phenotype data in Japanese cohorts but remains hypothesis-generating.
BACKGROUND: In the LQT2 form of long QT syndrome (LQTS), mutation sites are reported to correlate with clinical phenotypes in Caucasians, but the relationship in Asian patients remains unknown. The present study was designed to determine whether the location of KCNH2 mutations would influence the arrhythmic risk in LQT2 patients. METHODS AND RESULTS: In 118 genetically-confirmed LQT2 patients (69 families, 62 KCNH2 mutations), the ECG parameters, Schwartz scores, and the incidence of cardiac events, defined as syncope, aborted cardiac arrest, and sudden cardiac death, were evaluated. To examine the effect of mutation sites, the participants were divided accordingly: pore (n=56) and non-pore (n=62) groups. The corrected QTend interval was significantly greater in the pore than in the non-pore group (QTc; 522+/-63 ms vs 490+/-49 ms, p=0.002). In this study, the clinical course of each of the probands did not differ according to the mutation sites, whereas non-probands carrying the pore site mutation experienced their first cardiac events at significantly younger age than those with the non-pore site mutation (log-rank, p=0.0005). CONCLUSIONS: In a Japanese LQT2 cohort, family members with the pore site mutation were at higher arrhythmic risk than those with the non-pore site mutation.
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Nagaoka et al. (2008) conducted a cohort in LQT2 form of congenital long-QT syndrome (n=118). KCNH2 pore site mutation vs. KCNH2 non-pore site mutation was evaluated on Time to first cardiac event (syncope, aborted cardiac arrest, or sudden cardiac death) before age 50 years (p=0.049). KCNH2 pore site mutations were associated with a significantly younger age at first cardiac event compared to non-pore mutations, with the higher arrhythmic risk driven primarily by non-probands.
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