title: Genetic markers of repolarization and arrhythmic events after acute coronary syndromes.
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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand. Electronic address: n.earle@auckland.ac.nz.
authors.forename: N J
authors.initials: NJ
authors.lastname: Earle
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: K K
authors.initials: KK
authors.lastname: Poppe
authors.affiliation: Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: A P
authors.initials: AP
authors.lastname: Pilbrow
authors.affiliation: Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: V A
authors.initials: VA
authors.lastname: Cameron
authors.affiliation: Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: R W
authors.initials: RW
authors.lastname: Troughton
authors.affiliation: Greenlane Pediatric and Congenital Cardiac Services, Starship Childrens Hospital, Auckland, New Zealand.
authors.forename: J R
authors.initials: JR
authors.lastname: Skinner
authors.affiliation: Diagnostic Genetics, LabPlus, Auckland City Hospital, Auckland, New Zealand.
authors.forename: D R
authors.initials: DR
authors.lastname: Love
authors.affiliation: Department of Obstetrics and Gynecology, University of Auckland, Auckland, New Zealand.
authors.forename: A N
authors.initials: AN
authors.lastname: Shelling
authors.affiliation: Faculty of Social and Health Sciences, Unitec, Auckland, New Zealand.
authors.forename: G A
authors.initials: GA
authors.lastname: Whalley
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: C J
authors.initials: CJ
authors.lastname: Ellis
authors.affiliation: Christchurch Heart Institute, University of Otago, Christchurch, New Zealand; Cardiovascular Research Institute, National University of Singapore, Singapore.
authors.forename: A M
authors.initials: AM
authors.lastname: Richards
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: R N
authors.initials: RN
authors.lastname: Doughty
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D004247:DNA