Polymorphisms in the NOS1AP Gene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome

Objectives We investigated the role of nitric oxide 1 adaptor protein ( NOS1AP ) as a genetic modifier of long QT syndrome (LQTS). Background LQTS risk stratification is complicated by the phenotype variability that limits prediction of life-threatening arrhythmic events based on available metrics....

Full description

Saved in:

Bibliographic Details
Published in:	Journal of the American College of Cardiology 2010-06, Vol.55 (24), p.2745-2752
Main Authors:	Tomás, Marta, PhD, Napolitano, Carlo, MD, PhD, De Giuli, Luciana, PhD, Bloise, Raffaella, MD, Subirana, Isaac, MS, Malovini, Alberto, MS, Bellazzi, Riccardo, PhD, Arking, Dan E., PhD, Marban, Eduardo, MD, PhD, Chakravarti, Aravinda, PhD, Spooner, Peter M., PhD, Priori, Silvia G., MD, PhD
Format:	Article
Language:	eng
Subjects:	Adaptor Proteins, Signal Transducing - genetics Adult Biological and medical sciences Biomedical research Cardiac arrhythmia Cardiac dysrhythmias Cardiology. Vascular system Cardiovascular Deoxyribonucleic acid DNA DNA - genetics Electrocardiography Female Follow-Up Studies Genes Genetic Predisposition to Disease Genotype Haplotypes Heart Heart attacks Heart rate Humans Incidence Internal Medicine Long QT syndrome Long QT Syndrome - epidemiology Long QT Syndrome - genetics Long QT Syndrome - physiopathology Male Medical sciences Mutation Nitric oxide Polymerase Chain Reaction Polymorphism, Genetic Prognosis Prospective Studies Risk Factors Studies Time Factors
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Objectives We investigated the role of nitric oxide 1 adaptor protein ( NOS1AP ) as a genetic modifier of long QT syndrome (LQTS). Background LQTS risk stratification is complicated by the phenotype variability that limits prediction of life-threatening arrhythmic events based on available metrics. Thus, the identification of new markers is desirable. Recent studies have shown that NOS1AP variations in the gene modulate QT interval in healthy and 1 LQTS kindred, and occurrence of cardiac events in healthy subjects. Methods The study included 901 patients enrolled in a prospective LQTS registry. Three NOS1AP marker SNPs (rs4657139, rs16847548, and rs10494366) were genotyped to assess the effect of variant alleles on QTc and on the incidence of cardiac events. We quantified the association between variant alleles, QTc, and outcomes to assess whether NOS1AP is a useful risk stratifier in LQTS. Results Variant alleles tagged by SNPs rs4657139 and rs16847548 were associated with an average QTc prolongation of 7 and 8 ms, respectively (p < 0.05; p < 0.01); whereas rs4657139 and rs10494366 were associated with increased incidence of cardiac events (25.2% vs. 18.0%, p < 0.05 and 24.8% vs. 17.8% p < 0.05). Cox multivariate analysis identified rs10494366 minor allele as an independent prognostic marker among patients with QTc
ISSN:	0735-1097 1558-3597