KCNE1Polymorphism as Possible Modulator of Drug-Induced TdP

The goal of this study was to search for genetic variants that could be responsible for modifying the risk of drug-induced long QT syndrome (diLQTS). diLQTS is a relatively common adverse drug event and has been a leading cause for drug relabeling and withdrawal from the market. Our hypothesis, that variants in genes which regulate electrical properties in the heart modify the risk of diLQTS, was tested by genotyping patients of European descent at 1424 single nucleotide polymorphisms (SNPs) in 18 candidate genes. We found that the SNP KCNE1 D85N was highly predictive of diLQTS with an odds ratio of 9.0 (95% confidence interval: 3.5-22.9).]]>
Inclusion criteria for Cases: Cases were defined as those subjects ≥18 years of age at the time of an incident of drug-induced LQTS and/or TdP who had one of the following: An uncorrected QT interval ≥600 msec while on drug that decreased to <480 msec following withdrawal of drug; A change in uncorrected QT interval of at least 100 msec (either from the pre-exposure to the during-exposure ECG or from the during-exposure to the post-exposure ECG) with an uncorrected QT interval >480 msec while on drug; or An episode of ECG-documented TdP with a subsequent ECG with no evidence of TdP following withdrawal of drug. Exclusion criteria for Cases: Potassium level ≤3 mmol at onset of event (1 mEq = 1 mmol); Subarachnoid hemorrhage at onset of event; Cardiac bypass <24 hours before onset of event; Hospital admission diagnosis of hypothermia at time of event; Diagnosed with congenital LQTS prior to onset of event; Currently leukopenic (WBC<1000 cells/mL); Has had a non-autologous bone marrow transplant at anytime in the past. Inclusion criteria for Controls: 18 years of age or older; New start on QT-prolonging antiarrhythmic drug(s); Has not received a blood transfusion in the past 4 months. ]]>