Background: The KCNQ1 single nucleotide polymorphism (SNP), G643S, is known to be associated with secondary long QT syndrome (LQTS) and to cause a mild reduction in KCNQ1 current. However, the precise incidence and its association with QT intervals remain unknown in the greater cohort of the population in Japan.
Methods and results: The genotype was screened at codon 643 of KCNQ1 in 992 residents of a farming community. Eighty-eight individuals (female/male =52/36, 8.9%) were found to have a heterozygous G643S SNP. Matching both gender and age, we randomly selected 243 control (G643G) cases and compared the electrocardiogram parameters in both groups; QT, QTf (QT corrected by Fridericia's formula) intervals, the peak and the end of the T wave (Tpe) interval, and the Tpe/QT ratio. The latter 2 reflect the transmural dispersion of ventricular repolarization (TDR). In G643S carriers, both Tpe and Tpe/QT were significantly longer than in non-carriers, without significant QT prolongation. Both genders showed a tendency for an increase in QTf with aging. In females, both Tpe and Tpe/QT showed a similar significant increase with age, which was not observed in males.
Conclusions: In elderly females, G643S might be an independent risk factor for secondary LQTS by causing a greater TDR.