DOI: 10.1073/pnas.180223197. A common polymorphism associated with antibiotic-induced cardiac arrhythmia

A common polymorphism associated with antibiotic-induced cardiac arrhythmia

10.1073/pnas.180223197

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Drug-induced long QT syndrome (LQTS) is a prevalent disorder of uncertain etiology that predisposes to sudden death. KCNE2 encodes MinK-related peptide 1 (MiRP1), a subunit of the cardiac potassium channel I Kr that has been associated previously with inherited LQTS. Here, we examine KCNE2 in 98 patients with drug-induced LQTS, identifying three individuals with sporadic mutations and a patient with sulfamethoxazole-associated LQTS who carried a single-nucleotide polymorphism (SNP) found in ≈1.6% of the general population. While mutant channels showed diminished potassium flux at baseline and wild-type drug sensitivity, channels with the SNP were normal at baseline but inhibited by sulfamethoxazole at therapeutic levels that did not affect wild-type channels. We conclude that allelic variants of MiRP1 contribute to a significant fraction of cases of drug-induced LQTS through multiple mechanisms and that common sequence variations that increase the risk of life-threatening drug reactions can be clinically silent before drug exposure.

Bibliography

Sesti, F., Abbott, G. W., Wei, J., Murray, K. T., Saksena, S., Schwartz, P. J., Priori, S. G., Roden, D. M., George, A. L., & Goldstein, S. A. N. (2000). A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proceedings of the National Academy of Sciences, 97(19), 10613â10618.

Authors 10

Federico Sesti (first)
Geoffrey W. Abbott (additional)
Jian Wei (additional)
Katherine T. Murray (additional)
Sanjeev Saksena (additional)
Peter J. Schwartz (additional)
Silvia G. Priori (additional)
Dan M. Roden (additional)
Alfred L. George (additional)
Steve A. N. Goldstein (additional)

References 33 Referenced 376

10.1161/01.CIR.94.8.1996
10.1056/NEJM199705293362207
10.1126/science.272.5262.681
P J Schwartz, S G Priori, C Napolitano Cardiac Electrophysiology: From Cell to Bedside, eds D P Zipes, J Jalife (Saunders, Philadelphia), pp. 597–615 (2000). / Cardiac Electrophysiology: From Cell to Bedside by Schwartz P J (2000)
10.1038/376683a0
10.1016/0092-8674(95)90358-5
10.1038/ng0196-17
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B H Davies, K Rocchiccioli Pharmatherapeutica 3, 365–369 (1983). / Pharmatherapeutica by Davies B H (1983)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:34 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:23 a.m.)
Indexed	3 weeks ago (Aug. 6, 2025, 9:41 a.m.)
Issued	24 years, 11 months ago (Sept. 12, 2000)
Published	24 years, 11 months ago (Sept. 12, 2000)
Published Online	24 years, 11 months ago (Sept. 12, 2000)
Published Print	24 years, 11 months ago (Sept. 12, 2000)

Funders 0

None

BibTeX

@article{Sesti_2000, title={A common polymorphism associated with antibiotic-induced cardiac arrhythmia}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.180223197}, DOI={10.1073/pnas.180223197}, number={19}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sesti, Federico and Abbott, Geoffrey W. and Wei, Jian and Murray, Katherine T. and Saksena, Sanjeev and Schwartz, Peter J. and Priori, Silvia G. and Roden, Dan M. and George, Alfred L. and Goldstein, Steve A. N.}, year={2000}, month=sep, pages={10613–10618} }

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