title: Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction.
abstract: OBJECTIVE
  The rs10757278, rs1333049 and rs4977574 are single nucleotide polymorphisms (SNPs) of chromosome 9p21 locus associated with a prevalence of acute coronary syndromes (ACS). Reports concerning their association with long-term outcome after an ACS are equivocal. The aim of our study was to investigate the association of the 9p21.3 locus with 5-year overall mortality in patients with ST-elevation myocardial infarction (STEMI).
  
  
  METHODS
  We performed a retrospective analysis of data collected prospectively in 2 independent registries of consecutive patients with STEMI (derivation and validation group). Genotyping was performed with the TaqMan method. The analyzed end-point was total mortality.
  
  
  RESULTS
  The derivation group comprised 589 patients: 25.3% female (n = 149), mean age 62.4 ± 12.0 years, total 5-year mortality 16.6% (n = 98). When all the study group was analyzed, no significant differences in mortality were found between the genotypes. However, in high-risk patients (GRACE risk score ≥ 155 points, n = 238), homozygotes associated with higher risk for ACS had significantly better 5-year survival compared to other genotypes. The hazard ratio associated with the high-risk genotype (a homozygote of high risk for ACS or a heterozygote) was: HR = 2.2 (1.15-4.2) for the rs10757278 polymorphism, HR = 2.7 (95% CI 1.3-5.4) for the rs4977574 one and HR = 2.3 (1.2-4.5) for the rs1333049 one (Cox proportional hazards model). Survival analysis in the validation group (n = 365) showed a clear trend towards better prognosis in GG homozygotes of the rs10757278 SNP, which confirms our initial results (p = 0.09, log-rank test).
  
  
  CONCLUSIONS
  The 9p21.3 locus is associated with 5-year mortality in high-risk patients with STEMI. The genotypes associated with higher risk for ACS show a protective effect in terms of further survival (instead of a deteriorating prognosis, as reported previously). This finding, due to the very high size of the effect, could potentially be applied to clinical practice, if appropriate methods are elaborated.
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Szpakowicz
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kiliszek
authors.affiliation: Department of Forensic Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Pepinski
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Waszkiewicz
authors.affiliation: Laboratory of Molecular Biology, Institute of Cardiology, Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Franaszczyk
authors.affiliation: Department of Forensic Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Skawronska
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
authors.affiliation: Department of Forensic Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Niemcunowicz-Janica
authors.affiliation: Department of Invasive Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Dobrzycki
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opolski
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Włodzimierz Jerzy
authors.initials: WJ
authors.lastname: Musial
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Karol Adam
authors.initials: KA
authors.lastname: Kaminski
mesh_terms: D000368:Aged; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis
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