QT interval is linked to 2 long-QT syndrome loci in normal subjects

Background-The rate-corrected QT interval (QTc) is heritable, and the disco very of quantitative trait loci that influence the QTc would be an importan t step in identifying the genes responsible for life-threatening arrhythmia s in the general population. We studied 66 pairs of unselected normal dizyg otic (DZ) twin subjects and their parents in a sib-pair analysis. We tested for linkage of gene loci harboring genes known to cause the long-QT syndro me (LQT) to the quantitative trait QTc. Methods and Results-We found genetic variance on QRS duration, QRS axis, T- wave axis, and QTc. Women had a longer QTc than men. Microsatellite markers were tested in the vicinity of the gene loci for the 5 known LQT genes. We found significant linkage of QTc with the loci for LQT1 on chromosome 11 a nd LQT4 on chromosome 4 but not to LQT2, LQT3, or LQT5, We also found linka ge of the QRS axis with LQT2 and LQT3. Conclusions-We suggest that these quantitative trait loci may represent the presence of variations in LQT genes that could be important to the risk fo r rhythm disturbances in the general population.