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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

A common polymorphism associated with antibiotic-induced cardiac arrhythmia.

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 approximately 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.[1]


  1. A common polymorphism associated with antibiotic-induced cardiac arrhythmia. 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. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
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