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

Marta Tomás, Carlo Napolitano, Luciana De Giuli, Raffaella Bloise, Isaac Subirana, Alberto Malovini, Riccardo Bellazzi, Dan Arking, Eduardo Marban, Aravinda Chakravarti, Peter M. Spooner, Silvia G. Priori

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish (US)
Pages (from-to)2745-2752
Number of pages8
JournalJournal of the American College of Cardiology
Volume55
Issue number24
DOIs
StatePublished - Jun 15 2010

Fingerprint

Long QT Syndrome
Cardiac Arrhythmias
Alleles
Genes
Single Nucleotide Polymorphism
Romano-Ward Syndrome
Incidence
Registries
Healthy Volunteers
Nitric Oxide
Multivariate Analysis
Phenotype
Proteins

Keywords

  • cardiac arrhythmias
  • genetics
  • long QT syndrome
  • risk stratification
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Polymorphisms in the NOS1AP Gene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome. / Tomás, Marta; Napolitano, Carlo; De Giuli, Luciana; Bloise, Raffaella; Subirana, Isaac; Malovini, Alberto; Bellazzi, Riccardo; Arking, Dan; Marban, Eduardo; Chakravarti, Aravinda; Spooner, Peter M.; Priori, Silvia G.

In: Journal of the American College of Cardiology, Vol. 55, No. 24, 15.06.2010, p. 2745-2752.

Research output: Contribution to journalArticle

Tomás, M, Napolitano, C, De Giuli, L, Bloise, R, Subirana, I, Malovini, A, Bellazzi, R, Arking, D, Marban, E, Chakravarti, A, Spooner, PM & Priori, SG 2010, 'Polymorphisms in the NOS1AP Gene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome', Journal of the American College of Cardiology, vol. 55, no. 24, pp. 2745-2752. https://doi.org/10.1016/j.jacc.2009.12.065
Tomás, Marta ; Napolitano, Carlo ; De Giuli, Luciana ; Bloise, Raffaella ; Subirana, Isaac ; Malovini, Alberto ; Bellazzi, Riccardo ; Arking, Dan ; Marban, Eduardo ; Chakravarti, Aravinda ; Spooner, Peter M. ; Priori, Silvia G. / Polymorphisms in the NOS1AP Gene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome. In: Journal of the American College of Cardiology. 2010 ; Vol. 55, No. 24. pp. 2745-2752.
@article{ddeb7ecae2884ed89598aea0bb748842,
title = "Polymorphisms in the NOS1AP Gene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome",
abstract = "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",
keywords = "cardiac arrhythmias, genetics, long QT syndrome, risk stratification, single nucleotide polymorphisms",
author = "Marta Tom{\'a}s and Carlo Napolitano and {De Giuli}, Luciana and Raffaella Bloise and Isaac Subirana and Alberto Malovini and Riccardo Bellazzi and Dan Arking and Eduardo Marban and Aravinda Chakravarti and Spooner, {Peter M.} and Priori, {Silvia G.}",
year = "2010",
month = "6",
day = "15",
doi = "10.1016/j.jacc.2009.12.065",
language = "English (US)",
volume = "55",
pages = "2745--2752",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "24",

}

TY - JOUR

T1 - Polymorphisms in the NOS1AP Gene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome

AU - Tomás, Marta

AU - Napolitano, Carlo

AU - De Giuli, Luciana

AU - Bloise, Raffaella

AU - Subirana, Isaac

AU - Malovini, Alberto

AU - Bellazzi, Riccardo

AU - Arking, Dan

AU - Marban, Eduardo

AU - Chakravarti, Aravinda

AU - Spooner, Peter M.

AU - Priori, Silvia G.

PY - 2010/6/15

Y1 - 2010/6/15

N2 - 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

AB - 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

KW - cardiac arrhythmias

KW - genetics

KW - long QT syndrome

KW - risk stratification

KW - single nucleotide polymorphisms

UR - http://www.scopus.com/inward/record.url?scp=77953144675&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953144675&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2009.12.065

DO - 10.1016/j.jacc.2009.12.065

M3 - Article

VL - 55

SP - 2745

EP - 2752

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 24

ER -