Predicting Patient Response to the Antiarrhythmic Mexiletine Based on Genetic Variation.

ABSTRACT:

Rationale

Mutations in the SCN5A gene, encoding the α subunit of the Nav1.5 channel, cause a life-threatening form of cardiac arrhythmia, long QT syndrome type 3 (LQT3). Mexiletine, which is structurally related to the Na⁺ channel-blocking anesthetic lidocaine, is used to treat LQT3 patients. However, the patient response is variable, depending on the genetic mutation in SCN5A.

Objective

The goal of this study is to understand the molecular basis of patients' variable responses and build a predictive statistical model that can be used to personalize mexiletine treatment based on patient's genetic variant.

Methods and results

We monitored the cardiac Na⁺ channel voltage-sensing domain (VSD) conformational dynamics simultaneously with other gating

SUBMITTER: Zhu W 

PROVIDER: S-EPMC6588292 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature