Journal of Molecular Medicine

, Volume 82, Issue 3, pp 182–188 | Cite as

Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients

  • Aimée D. C. Paulussen
  • Ronaldus A. H. J. Gilissen
  • Martin Armstrong
  • Pieter A. Doevendans
  • Peter Verhasselt
  • Hubert J. M. Smeets
  • Eric Schulze-Bahr
  • Wilhelm Haverkamp
  • Günter Breithardt
  • Nadine Cohen
  • Jeroen AerssensEmail author
Original Article


Administration of specific drugs may occasionally induce acquired long QT syndrome (aLQTS), a disorder that predisposes to ventricular arrhythmias, typically of the torsade de pointes (TdP) type, and sudden cardiac death. “Forme fruste” mutations in congenital LQTS (cLQTS) genes have been reported repeatedly as the underlying cause of aLQTS, and are therefore considered as an important risk factor. We evaluated the impact of genetic susceptibility for aLQTS through mutations in cLQTS genes. Five cLQTS genes (KCNH2, KCNQ1, SCN5A, KCNE1, KCNE2) were thoroughly screened for genetic variations in 32 drug-induced aLQTS patients with confirmed TdP and 32 healthy individuals. Missense forme frust mutations were identified in four aLQTS patients: D85N in KCNE1 (two cases), T8A in KCNE2, and P347S in KCNH2. Three other missense variations were found both in patients and controls, and are thus unlikely to significantly influence aLQTS susceptibility. In addition, 13 silent and six intronic variations were detected, four of which were found in a single aLQTS patient but not in the controls. We conclude that missense mutations in the examined cLQTS genes explain only a minority of aLQTS cases.


Long QT syndrome Drug-induced Arrhythmia Mutation analysis 



Congenital long QT syndrome


Acquired long QT syndrome


Torsade de pointes




Corrected QT


Polymerase chain reaction


Linkage disequilibrium



We thank Rosemary Zvonar (Department of Pharmaceutical Services, The Ottawa Hospital, Canada) for providing a patient sample. E. Schulze-Bahr and W. Haverkamp are supported by grants from the Deutsche Forschungsgemeinschaft (grants Schu1082/2–2 and SFB556-A1) and the Fondation Leducq (France). P. Doevendans is supported by the Interuniversitary Cardiology Institute (The Netherlands).


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Aimée D. C. Paulussen
    • 1
  • Ronaldus A. H. J. Gilissen
    • 1
  • Martin Armstrong
    • 1
  • Pieter A. Doevendans
    • 3
  • Peter Verhasselt
    • 2
  • Hubert J. M. Smeets
    • 4
  • Eric Schulze-Bahr
    • 5
  • Wilhelm Haverkamp
    • 5
  • Günter Breithardt
    • 5
  • Nadine Cohen
    • 1
  • Jeroen Aerssens
    • 1
    Email author
  1. 1.Department of PharmacogenomicsJohnson & Johnson Pharmaceutical Research and DevelopmentBeerseBelgium
  2. 2.Department of Functional GenomicsJohnson & Johnson Pharmaceutical Research and DevelopmentBeerseBelgium
  3. 3.Department of CardiologyAcademic HospitalMaastrichtThe Netherlands
  4. 4.Department of Genetics and Cell BiologyCardiovascular Research Institute Maastricht (CARIM)MaastrichtThe Netherlands
  5. 5.Department of Cardiology and Angiology, Hospital of the Westfalian Wilhelms-University, Institute for Arteriosclerosis Research University of MünsterMünsterGermany

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