N J Earle1, K K Poppe2, A P Pilbrow3, V A Cameron3, R W Troughton3, J R Skinner4, D R Love5, A N Shelling6, G A Whalley7, C J Ellis2, A M Richards8, R N Doughty2. 1. Department of Medicine, University of Auckland, Auckland, New Zealand. Electronic address: n.earle@auckland.ac.nz. 2. Department of Medicine, University of Auckland, Auckland, New Zealand. 3. Christchurch Heart Institute, University of Otago, Christchurch, New Zealand. 4. Greenlane Pediatric and Congenital Cardiac Services, Starship Childrens Hospital, Auckland, New Zealand. 5. Diagnostic Genetics, LabPlus, Auckland City Hospital, Auckland, New Zealand. 6. Department of Obstetrics and Gynecology, University of Auckland, Auckland, New Zealand. 7. Faculty of Social and Health Sciences, Unitec, Auckland, New Zealand. 8. Christchurch Heart Institute, University of Otago, Christchurch, New Zealand; Cardiovascular Research Institute, National University of Singapore, Singapore.
Abstract
BACKGROUND: There is a genetic contribution to the risk of ventricular arrhythmias in survivors of acute coronary syndromes (ACS). We wished to explore the role of 33 candidate single nucleotide polymorphisms (SNPs) in prolonged repolarization and sudden death in patients surviving ACS. METHODS: A total of 2,139 patients (1680 white ethnicity) surviving an admission for ACS were enrolled in the prospective Coronary Disease Cohort Study. Extensive clinical, echocardiographic, and neurohormonal data were collected for 12 months, and clinical events were recorded for a median of 5 years. Each SNP was assessed for association with sudden cardiac death (SCD)/cardiac arrest (CA) and prolonged repolarization at 3 time-points: index admission, 1 month, and 12 months postdischarge. RESULTS: One hundred six SCD/CA events occurred during follow-up (6.3%). Three SNPs from 3 genes (rs17779747 [KCNJ2], rs876188 [C14orf64], rs3864180 [GPC5]) were significantly associated with SCD/CA in multivariable models (after correction for multiple testing); the minor allele of rs17779747 with a decreased risk (hazard ratio [HR] 0.68 per copy of the minor allele, 95% CI 0.50-0.92, P = .012), and rs876188 and rs386418 with an increased risk (HR 1.52 [95% CI 1.10-2.09, P = .011] and HR 1.34 [95% CI 1.04-1.82, P = .023], respectively). At 12 months postdischarge, rs10494366 and rs12143842 (NOS1AP) were significant predictors of prolonged repolarization (HR 1.32 [95% CI 1.04-1.67, P = .022] and HR 1.30 [95% CI 1.01-1.66, P = .038], respectively), but not at earlier time-points. CONCLUSION: Three SNPs were associated with SCD/CA. Repolarization time was associated with variation in the NOS1AP gene. This study demonstrates a possible role for SNPs in risk stratification for arrhythmic events after ACS.
BACKGROUND: There is a genetic contribution to the risk of ventricular arrhythmias in survivors of acute coronary syndromes (ACS). We wished to explore the role of 33 candidate single nucleotide polymorphisms (SNPs) in prolonged repolarization and sudden death in patients surviving ACS. METHODS: A total of 2,139 patients (1680 white ethnicity) surviving an admission for ACS were enrolled in the prospective Coronary Disease Cohort Study. Extensive clinical, echocardiographic, and neurohormonal data were collected for 12 months, and clinical events were recorded for a median of 5 years. Each SNP was assessed for association with sudden cardiac death (SCD)/cardiac arrest (CA) and prolonged repolarization at 3 time-points: index admission, 1 month, and 12 months postdischarge. RESULTS: One hundred six SCD/CA events occurred during follow-up (6.3%). Three SNPs from 3 genes (rs17779747 [KCNJ2], rs876188 [C14orf64], rs3864180 [GPC5]) were significantly associated with SCD/CA in multivariable models (after correction for multiple testing); the minor allele of rs17779747 with a decreased risk (hazard ratio [HR] 0.68 per copy of the minor allele, 95% CI 0.50-0.92, P = .012), and rs876188 and rs386418 with an increased risk (HR 1.52 [95% CI 1.10-2.09, P = .011] and HR 1.34 [95% CI 1.04-1.82, P = .023], respectively). At 12 months postdischarge, rs10494366 and rs12143842 (NOS1AP) were significant predictors of prolonged repolarization (HR 1.32 [95% CI 1.04-1.67, P = .022] and HR 1.30 [95% CI 1.01-1.66, P = .038], respectively), but not at earlier time-points. CONCLUSION: Three SNPs were associated with SCD/CA. Repolarization time was associated with variation in the NOS1AP gene. This study demonstrates a possible role for SNPs in risk stratification for arrhythmic events after ACS.
Authors: Cameron J Lacey; Kit Doudney; Paul G Bridgman; Peter M George; Roger T Mulder; Julie J Zarifeh; Bridget Kimber; Murray J Cadzow; Michael A Black; Tony R Merriman; Klaus Lehnert; Vivienne M Bickley; John F Pearson; Vicky A Cameron; Martin A Kennedy Journal: Sci Rep Date: 2018-05-15 Impact factor: 4.379
Authors: Philip D Adamson; David McAllister; Anna Pilbrow; John William Pickering; Katrina Poppe; Anoop Shah; Gillian Whalley; Chris Ellis; Nicholas L Mills; David E Newby; Chris Pemberton; Richard W Troughton; Rob N Doughty; A Mark Richards Journal: Heart Date: 2019-07-23 Impact factor: 7.365