Referenced in: none

Automatically associated channels: Kv7.1

Title: A common polymorphism associated with antibiotic-induced cardiac arrhythmia.

Authors: F Sesti, G W Abbott, J Wei, K T Murray, S Saksena, P J Schwartz, S G Priori, D M Roden, A L George, S A Goldstein

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2000 Sep 12 , 97, 10613-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/10984545

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 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.