Common Ancestry-Specific Ion Channel Variants Predispose to Drug-Induced Arrhythmias.

ABSTRACT:

Background

Multiple reports associate the cardiac sodium channel gene (SCN5A) variants S1103Y and R1193Q with type 3 congenital long QT syndrome and drug-induced long QT syndrome. These variants are too common in ancestral populations to be highly arrhythmogenic at baseline, however: S1103Y allele frequency is 8.1% in African Americans and R1193Q 6.1% in East Asians. R1193Q is known to increase late sodium current (I_Na-L) in cardiomyocytes derived from induced pluripotent stem cells but the role of these variants in modulating repolarization remains poorly understood.

Methods

We determined the effect of S1103Y on QT intervals among African-American participants in a large electronic health record. Using cardiomyocytes derived from induced pluripotent

SUBMITTER: Wada Y 

PROVIDER: S-EPMC8852297 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature