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(Circulation. 1999;99:3161-3164.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

QT Interval Is Linked to 2 Long-QT Syndrome Loci in Normal Subjects

Andreas Busjahn, PhD; Hans Knoblauch, MD; Hans-Dieter Faulhaber, MD; Thomas Boeckel, MD; Magda Rosenthal; Regina Uhlmann; Margret Hoehe, MD; Herbert Schuster, MD; Friedrich C. Luft, MD, FRCP (Edin)

From the Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Germany.

Correspondence to Friedrich C. Luft, Franz Volhard Clinic, Wiltberg Strasse 50, 13122 Berlin, Germany. E-mail luft{at}fvk-berlin.de

Background—The rate-corrected QT interval (QTc) is heritable, and the discovery of quantitative trait loci that influence the QTc would be an important step in identifying the genes responsible for life-threatening arrhythmias in the general population. We studied 66 pairs of unselected normal dizygotic (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 syndrome (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 and LQT4 on chromosome 4 but not to LQT2, LQT3, or LQT5. We also found linkage 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 for rhythm disturbances in the general population.

Key Words: molecular biology • long-QT syndrome • intervals • genetics • electrocardiography

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