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A common polymorphism associated with antibiotic-induced cardiac arrhythmia
Open accessAbstract
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.
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Citations
Cited by
Drug-induced prolongation of the QT interval
Roden, D. M. (2004) · New England Journal of Medicine · doi:10.1056/nejmra032426 · Cited by 1,965
Self-citationPharmacogenomics — Drug Disposition, Drug Targets, and Side Effects
Evans, W. E., & McLeod, H. L. (2003) · New England Journal of Medicine · doi:10.1056/nejmra020526 · Cited by 1,769
Allelic Variants in Long-QT Disease Genes in Patients With Drug-Associated Torsades de Pointes
Yang, P., Kanki, H., Drolet, B., Yang, T., Wei, J., Viswanathan, P. C., Hohnloser, S. H., Shimizu, W., Schwartz, P. J., Stanton, M., et al. (2002) · Circulation · doi:10.1161/01.cir.0000014448.19052.4c · Cited by 554
Self-citationNabel, E. G. (2003) · New England Journal of Medicine · doi:10.1056/nejmra035098 · Cited by 431
Ashcroft, F. M. (2006) · Nature · doi:10.1038/nature04707 · Cited by 403
Metadata
- Authors
- 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.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-09-12
- Volume
- 97
- Issue
- 19
- Pages
- 10613-10618
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2093638125
- Cited by
- 479
- References
- 0
- FWCI
- 30.79
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: A common polymorphism associated with antibiotic-induced cardiac arrhythmia. https://app.cochat.ai/papers/10.1073/pnas.180223197
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- 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. https://doi.org/10.1073/pnas.180223197
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