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Journal Article
Research Support, Non-U.S. Gov't
Review
From GWAS to function: genetic variation in sodium channel gene enhancer influences electrical patterning.
Trends in Cardiovascular Medicine 2014 April
The electrical activity of the heart depends on the correct interplay between key transcription factors and cis-regulatory elements, which together regulate the proper heterogeneous expression of genes encoding for ion channels and other proteins. Genome-wide association studies of ECG parameters implicated genetic variants in the genes for these factors and ion channels modulating conduction and depolarization. Here, we review recent insights into the regulation of localized expression of ion channel genes and the mechanism by which a single-nucleotide polymorphism (SNP) associated with alterations in cardiac conduction patterns in humans affects the transcriptional regulation of the sodium channel genes, SCN5A and SCN10A. The identification of regulatory elements of electrical activity genes helps to explain the impact of genetic variants in non-coding regulatory DNA sequences on regulation of cardiac conduction and the predisposition for cardiac arrhythmias.
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