Allelic variants of SCN5A and risk of sudden cardiac arrest in patients with coronary artery disease

Eric Stecker, Megan Sono, Erin Wallace, Karen Gunson, Jonathan Jui, Sumeet S. Chugh

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Most sudden cardiac arrests occur in patients who have associated significant coronary artery disease (CAD), but current methods of risk stratification are inadequate. Objectives: The purpose of this study was to evaluate whether allelic variation of SCN5A could determine risk of sudden cardiac arrest among patients with CAD. Methods: This case-control study was conducted as part of the ongoing Oregon Sudden Unexpected Death Study (Ore-SUDS). Cases of sudden cardiac arrest with associated CAD were identified among residents of Multnomah County, Oregon (population 660,486). Geographically matched control subjects had significant CAD but no history of cardiac arrest, ventricular arrhythmia, or syncope. DNA was extracted from blood samples, and all 28 exons of SCN5A were screened for allelic variants using denaturing high-performance liquid chromatography. All identified variants were confirmed by direct sequencing. Results: Sixty-seven cases (mean age 65 ± 13 years, 18% female) and 91 controls (mean age 66 ± 12 years, 30% female) were compared. Race was known in 94% of all patients; 92% of case subjects and 89% of control subjects were Caucasian. No patient had clinically manifest familial long QT syndrome. Nonsynonymous nucleotide changes were found in 4% of cases and 1% of controls (P = .31), with one novel mutation (G1291A) identified in one case subject. Synonymous nucleotide changes were found in 27% of cases and 21% of controls (P = .45). Conclusion: The overall prevalence of amino acid-altering polymorphisms of the SCN5A gene was relatively low in both groups. Allelic variants of SCN5A did not contribute to risk of sudden cardiac arrest in this primarily Caucasian population with significant CAD.

Original languageEnglish (US)
Pages (from-to)697-700
Number of pages4
JournalHeart Rhythm
Volume3
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Sudden Cardiac Death
Coronary Artery Disease
Nucleotides
Long QT Syndrome
Syncope
Sudden Death
Heart Arrest
Population
Case-Control Studies
Cardiac Arrhythmias
Exons
High Pressure Liquid Chromatography
Amino Acids
Mutation
DNA
Genes

Keywords

  • Genetics
  • Genome
  • Population
  • Risk
  • Stratification
  • Sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Allelic variants of SCN5A and risk of sudden cardiac arrest in patients with coronary artery disease. / Stecker, Eric; Sono, Megan; Wallace, Erin; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S.

In: Heart Rhythm, Vol. 3, No. 6, 06.2006, p. 697-700.

Research output: Contribution to journalArticle

Stecker, Eric ; Sono, Megan ; Wallace, Erin ; Gunson, Karen ; Jui, Jonathan ; Chugh, Sumeet S. / Allelic variants of SCN5A and risk of sudden cardiac arrest in patients with coronary artery disease. In: Heart Rhythm. 2006 ; Vol. 3, No. 6. pp. 697-700.
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abstract = "Background: Most sudden cardiac arrests occur in patients who have associated significant coronary artery disease (CAD), but current methods of risk stratification are inadequate. Objectives: The purpose of this study was to evaluate whether allelic variation of SCN5A could determine risk of sudden cardiac arrest among patients with CAD. Methods: This case-control study was conducted as part of the ongoing Oregon Sudden Unexpected Death Study (Ore-SUDS). Cases of sudden cardiac arrest with associated CAD were identified among residents of Multnomah County, Oregon (population 660,486). Geographically matched control subjects had significant CAD but no history of cardiac arrest, ventricular arrhythmia, or syncope. DNA was extracted from blood samples, and all 28 exons of SCN5A were screened for allelic variants using denaturing high-performance liquid chromatography. All identified variants were confirmed by direct sequencing. Results: Sixty-seven cases (mean age 65 ± 13 years, 18{\%} female) and 91 controls (mean age 66 ± 12 years, 30{\%} female) were compared. Race was known in 94{\%} of all patients; 92{\%} of case subjects and 89{\%} of control subjects were Caucasian. No patient had clinically manifest familial long QT syndrome. Nonsynonymous nucleotide changes were found in 4{\%} of cases and 1{\%} of controls (P = .31), with one novel mutation (G1291A) identified in one case subject. Synonymous nucleotide changes were found in 27{\%} of cases and 21{\%} of controls (P = .45). Conclusion: The overall prevalence of amino acid-altering polymorphisms of the SCN5A gene was relatively low in both groups. Allelic variants of SCN5A did not contribute to risk of sudden cardiac arrest in this primarily Caucasian population with significant CAD.",
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N2 - Background: Most sudden cardiac arrests occur in patients who have associated significant coronary artery disease (CAD), but current methods of risk stratification are inadequate. Objectives: The purpose of this study was to evaluate whether allelic variation of SCN5A could determine risk of sudden cardiac arrest among patients with CAD. Methods: This case-control study was conducted as part of the ongoing Oregon Sudden Unexpected Death Study (Ore-SUDS). Cases of sudden cardiac arrest with associated CAD were identified among residents of Multnomah County, Oregon (population 660,486). Geographically matched control subjects had significant CAD but no history of cardiac arrest, ventricular arrhythmia, or syncope. DNA was extracted from blood samples, and all 28 exons of SCN5A were screened for allelic variants using denaturing high-performance liquid chromatography. All identified variants were confirmed by direct sequencing. Results: Sixty-seven cases (mean age 65 ± 13 years, 18% female) and 91 controls (mean age 66 ± 12 years, 30% female) were compared. Race was known in 94% of all patients; 92% of case subjects and 89% of control subjects were Caucasian. No patient had clinically manifest familial long QT syndrome. Nonsynonymous nucleotide changes were found in 4% of cases and 1% of controls (P = .31), with one novel mutation (G1291A) identified in one case subject. Synonymous nucleotide changes were found in 27% of cases and 21% of controls (P = .45). Conclusion: The overall prevalence of amino acid-altering polymorphisms of the SCN5A gene was relatively low in both groups. Allelic variants of SCN5A did not contribute to risk of sudden cardiac arrest in this primarily Caucasian population with significant CAD.

AB - Background: Most sudden cardiac arrests occur in patients who have associated significant coronary artery disease (CAD), but current methods of risk stratification are inadequate. Objectives: The purpose of this study was to evaluate whether allelic variation of SCN5A could determine risk of sudden cardiac arrest among patients with CAD. Methods: This case-control study was conducted as part of the ongoing Oregon Sudden Unexpected Death Study (Ore-SUDS). Cases of sudden cardiac arrest with associated CAD were identified among residents of Multnomah County, Oregon (population 660,486). Geographically matched control subjects had significant CAD but no history of cardiac arrest, ventricular arrhythmia, or syncope. DNA was extracted from blood samples, and all 28 exons of SCN5A were screened for allelic variants using denaturing high-performance liquid chromatography. All identified variants were confirmed by direct sequencing. Results: Sixty-seven cases (mean age 65 ± 13 years, 18% female) and 91 controls (mean age 66 ± 12 years, 30% female) were compared. Race was known in 94% of all patients; 92% of case subjects and 89% of control subjects were Caucasian. No patient had clinically manifest familial long QT syndrome. Nonsynonymous nucleotide changes were found in 4% of cases and 1% of controls (P = .31), with one novel mutation (G1291A) identified in one case subject. Synonymous nucleotide changes were found in 27% of cases and 21% of controls (P = .45). Conclusion: The overall prevalence of amino acid-altering polymorphisms of the SCN5A gene was relatively low in both groups. Allelic variants of SCN5A did not contribute to risk of sudden cardiac arrest in this primarily Caucasian population with significant CAD.

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