Common Coding Variants in SCN10A Are Associated With the Nav1.8 Late Current and Cardiac Conduction

Circulation. Genomic and Precision Medicine
Vincenzo MacriPatrick T Ellinor

Abstract

Genetic variants at the SCN5A/SCN10A locus are strongly associated with electrocardiographic PR and QRS intervals. While SCN5A is the canonical cardiac sodium channel gene, the role of SCN10A in cardiac conduction is less well characterized. We sequenced the SCN10A locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology. We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium (r  2=0.86) with each other to be the strongest signals for PR (rs10428132, β=-4.74, P=1.52×10-14) and QRS intervals (rs6599251, QRS β=-0.73; P=1.2×10-4), respectively. Although these variants were not associated with SCN5A or SCN10A expression in human atrial tissue (n=490), they were in high linkage disequilibrium (r  2≥0.72) with a common SCN10A missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluste...Continue Reading

References

Jul 27, 2000·The New England Journal of Medicine·P J SchwartzR Bloise
Mar 20, 2001·American Journal of Human Genetics·M StephensP Donnelly
Jun 28, 2002·Neuron·Christoph LossinAlfred L George
Jul 11, 2006·The American Journal of Medicine·Aseem D DesaiVictor F Froelicher
Aug 2, 2008·Science·Bjarke AbrahamsenJohn N Wood
Jun 25, 2009·JAMA : the Journal of the American Medical Association·Susan ChengThomas J Wang
Jan 12, 2010·Nature Genetics·Arne PfeuferSusan R Heckbert
Jan 12, 2010·Nature Genetics·John C ChambersJaspal S Kooner
Jan 12, 2010·Nature Genetics·Hilma HolmKari Stefansson
Jun 8, 2011·International Heart Journal·Paul FacerPraveen Anand
Jun 19, 2012·The Journal of Clinical Investigation·Malou van den BoogaardVincent M Christoffels
Jun 26, 2012·The Journal of Clinical Investigation·David E ArnoldsIvan P Moskowitz
Jul 24, 2012·Circulation Research·Barry London
Mar 20, 2014·The Journal of Clinical Investigation·Malou van den BoogaardIvan P Moskowitz
Jul 7, 2014·Journal of the American College of Cardiology·Dan HuCharles Antzelevitch
Nov 4, 2016·Journal of the American Heart Association·Dina Myers StroudDan M Roden
Nov 4, 2016·Journal of the American Heart Association·XiaoMeng ChenDan Hu

❮ Previous
Next ❯

Citations

Jan 10, 2020·Cardiovascular Drugs and Therapy·Simona CasiniCarol Ann Remme
May 20, 2020·Cardiovascular Research·Charlotte GlingeConnie R Bezzina
Jul 12, 2019·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Michelle M MonaskyCarlo Pappone
Jan 20, 2020·Cardiovascular Drugs and Therapy·Katja E Odening
Apr 30, 2021·Circulation·Joyce C K ManVincent M Christoffels
Jul 28, 2021·Human Molecular Genetics·Yan HuangDan Hu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Conduction System

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Discover the latest research on the cardiac conduction system here.

Cardiac Electrophysiology

Cardiac electrophysiology is the study of electrical activities of the heart and includes the assessment, diagnosis, and treatment of cardiac events. Find the latest research on cardiac electrophysiology here.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

Related Papers

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology
Jessica T DelaneyDawood Darbar
© 2022 Meta ULC. All rights reserved