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Trends Cardiovasc Med. 2014 Apr;24(3):99-104. doi: 10.1016/j.tcm.2013.09.001. Epub 2013 Dec 17.

From GWAS to function: genetic variation in sodium channel gene enhancer influences electrical patterning.

Author information

1
Department of Anatomy, Embryology and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, the Netherlands.
2
Department of Anatomy, Embryology and Physiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, the Netherlands. Electronic address: v.m.christoffels@amc.uva.nl.

Abstract

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.

PMID:
24360055
DOI:
10.1016/j.tcm.2013.09.001
[Indexed for MEDLINE]

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