Analysis for Genetic Modifiers of Disease Severity in Patients With Long-QT Syndrome Type 2

Circulation. Cardiovascular Genetics
Iris C R M KolderConnie R Bezzina

Abstract

Considerable interest exists in the identification of genetic modifiers of disease severity in the long-QT syndrome (LQTS) as their identification may contribute to refinement of risk stratification. We searched for single-nucleotide polymorphisms (SNPs) that modulate the corrected QT (QTc)-interval and the occurrence of cardiac events in 639 patients harboring different mutations in KCNH2. We analyzed 1201 SNPs in and around 18 candidate genes, and in another approach investigated 22 independent SNPs previously identified as modulators of QTc-interval in genome-wide association studies in the general population. In an analysis for quantitative effects on the QTc-interval, 3 independent SNPs at NOS1AP (rs10494366, P=9.5×10(-8); rs12143842, P=4.8×10(-7); and rs2880058, P=8.6×10(-7)) were strongly associated with the QTc-interval with marked effects (>12 ms/allele). Analysis of patients versus general population controls uncovered enrichment of QTc-prolonging alleles in patients for 2 SNPs, located respectively at NOS1AP (rs12029454; odds ratio, 1.85; 95% confidence interval, 1.32-2.59; P=3×10(-4)) and KCNQ1 (rs12576239; odds ratio, 1.84; 95% confidence interval, 1.31-2.60; P=5×10(-4)). An analysis of the cumulative effect of the...Continue Reading

References

Sep 5, 2002·Circulation·Naomasa MakitaAkira Kitabatake
May 9, 2003·The New England Journal of Medicine·Silvia G PrioriDonata Cappelletti
Mar 31, 2004·Circulation·Peter WestenskowMichael C Sanguinetti
Oct 26, 2005·Nature Genetics·Paul I W de BakkerDavid Altshuler
May 2, 2006·Nature Genetics·Dan E ArkingAravinda Chakravarti
Mar 1, 2008·Journal of the American College of Cardiology·Peter J SchwartzPaul A Brink
Mar 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kuan-Cheng ChangEduardo Marbán
Mar 24, 2009·Nature Genetics·Christopher Newton-ChehBruno H Ch Stricker
Mar 24, 2009·Nature Genetics·Arne PfeuferAravinda Chakravarti
Oct 14, 2009·Circulation·Lia CrottiAlfred L George
Nov 21, 2009·Journal of the American College of Cardiology·Wataru ShimizuScott McNitt
Dec 25, 2009·Circulation. Cardiovascular Genetics·Fabio MarroniUNKNOWN EUROSPAN Consortium
Jan 12, 2010·Nature Genetics·John C ChambersJaspal S Kooner
Jun 12, 2010·Journal of the American College of Cardiology·Marta TomásSilvia G Priori
May 21, 2013·Journal of the American College of Cardiology·Peter J SchwartzArthur A M Wilde
May 30, 2013·European Journal of Human Genetics : EJHG·Dorret I BoomsmaCornelia M van Duijn
Jul 17, 2013·Circulation. Cardiovascular Genetics·Sabine DuchateletPeter J Schwartz

❮ Previous
Next ❯

Citations

Sep 8, 2015·Trends in Cardiovascular Medicine·Pieter G Postema
Jul 28, 2016·International Journal of Legal Medicine·Iliana TzimasMicaela Poetsch
Feb 2, 2018·Nature Reviews. Cardiology·Charlotte FarahJean-Luc Balligand
Jun 18, 2015·Circulation. Cardiovascular Genetics·Martin R Pollak
Oct 8, 2017·Circulation. Cardiovascular Genetics·Takeshi Aiba, Atsushi Takahashi
Jun 26, 2015·Journal of Human Genetics·Yukiko Nakano, Wataru Shimizu
Nov 24, 2016·Clinical Chemistry·Roddy Walsh, Stuart A Cook
Sep 24, 2016·Journal of Cardiovascular Medicine·Valentina FavalliEloisa Arbustini
Apr 1, 2020·Cardiovascular Research·Lia CrottiMichael C Sanguinetti
May 20, 2020·Cardiovascular Research·Charlotte GlingeConnie R Bezzina
Sep 17, 2020·Circulation. Genomic and Precision Medicine·Asami KashiwaWataru Shimizu
Sep 15, 2018·European Heart Journal·Peter J SchwartzAlfred L George
Feb 23, 2020·Circulation·Jodie Ingles, Christopher Semsarian
Jul 28, 2020·Circulation Research·M Benjamin ShoemakerMarco V Perez
May 1, 2020·European Heart Journal·Roddy WalshConnie R Bezzina
Feb 19, 2021·Journal of the American Heart Association·Arja S Vink, Pieter G Postema

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.