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Updated: Apr 4, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

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NOS1AP Polymorphisms Modify QTc Interval Duration But Not Cardiac Arrest Risk in Hypertrophic Cardiomyopathy

Nikki Earle1, Jodie Ingles2,3,4, Richard D Bagnall2,3

  • 1Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Journal of Cardiovascular Electrophysiology
|September 3, 2015
PubMed

Insights

Genetic variations in the NOS1AP gene affect corrected QT interval (QTc) duration in hypertrophic cardiomyopathy (HCM) patients. However, these single nucleotide polymorphisms (SNPs) were not directly linked to sudden cardiac death (SCD) risk.

Area of Science:

  • Cardiology
  • Genetics
  • Molecular Biology

Background:

  • Sudden cardiac death (SCD) risk prediction in hypertrophic cardiomyopathy (HCM) is challenging.
  • Corrected QT interval (QTc) duration is a known risk factor for cardiac events.
  • Single nucleotide polymorphisms (SNPs) are implicated in QTc length and SCD risk.

Purpose of the Study:

  • Investigate the association between 21 candidate SNPs, QTc duration, and SCD events in HCM patients.
  • Determine if specific SNPs influence QTc prolongation or SCD risk in this population.

Main Methods:

  • A registry-based study of HCM patients with available ECG, medical history, SCD event data, and DNA.
  • Logistic regression analysis to assess associations between SNPs and prolonged QTc (≥440 ms) or SCD events.
  • Multivariate analysis adjusted for clinical factors.

Main Results:

  • A QTc ≥ 500 ms was associated with SCD events (OR = 4.0, P = 0.016).
  • Two NOS1AP gene SNPs (rs10494366 and rs12143842) were significantly associated with prolonged QTc in Caucasian HCM patients (P = 0.022 and P = 0.020).
  • No direct association was found between any tested SNPs and SCD events.

Conclusions:

  • SNPs within the NOS1AP gene play a role in determining QTc interval duration in HCM.
  • This study did not establish a direct causal link between these NOS1AP SNPs and the risk of sudden cardiac death in HCM patients.
Abstract

Keywords:
QTc intervalhypertrophic cardiomyopathysingle nucleotide polymorphismssudden death

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