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.
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.
Authors: H Knoblauch; B Müller-Myhsok; A Busjahn; L Ben Avi; S Bähring; H Baron; S C Heath; R Uhlmann; H D Faulhaber; S Shpitzen; A Aydin; A Reshef; M Rosenthal; O Eliav; A Mühl; A Lowe; D Schurr; D Harats; E Jeschke; Y Friedlander; H Schuster; F C Luft; E Leitersdorf Journal: Am J Hum Genet Date: 2000-01 Impact factor: 11.025
Authors: L Gouas; V Nicaud; S Chaouch; M Berthet; A Forhan; J Tichet; L Tiret; B Balkau; P Guicheney Journal: Eur J Hum Genet Date: 2007-05-30 Impact factor: 4.246
Authors: Sara Mutikainen; Alfredo Ortega-Alonso; Markku Alén; Jaakko Kaprio; Jouko Karjalainen; Taina Rantanen; Urho M Kujala Journal: Ann Noninvasive Electrocardiol Date: 2009-01 Impact factor: 1.468
Authors: Ilja M Nolte; Chris Wallace; Stephen J Newhouse; Daryl Waggott; Jingyuan Fu; Nicole Soranzo; Rhian Gwilliam; Panos Deloukas; Irina Savelieva; Dongling Zheng; Chrysoula Dalageorgou; Martin Farrall; Nilesh J Samani; John Connell; Morris Brown; Anna Dominiczak; Mark Lathrop; Eleftheria Zeggini; Louise V Wain; Christopher Newton-Cheh; Mark Eijgelsheim; Kenneth Rice; Paul I W de Bakker; Arne Pfeufer; Serena Sanna; Dan E Arking; Folkert W Asselbergs; Tim D Spector; Nicholas D Carter; Steve Jeffery; Martin Tobin; Mark Caulfield; Harold Snieder; Andrew D Paterson; Patricia B Munroe; Yalda Jamshidi Journal: PLoS One Date: 2009-07-09 Impact factor: 3.240