Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction

Anna Szpakowicz; Marek Kiliszek; Witold Pepinski; Ewa Waszkiewicz; Maria Franaszczyk; Małgorzata Skawronska; Rafal Ploski; Anna Niemcunowicz-Janica; Sławomir Dobrzycki; Grzegorz Opolski; Włodzimierz Jerzy Musial; Karol Adam Kaminski

doi:10.1371/journal.pone.0104635

Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction

PLoS One. 2014 Aug 8;9(8):e104635. doi: 10.1371/journal.pone.0104635. eCollection 2014.

Affiliations

¹ Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
² Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
³ Department of Forensic Medicine, Medical University of Bialystok, Bialystok, Poland.
⁴ Laboratory of Molecular Biology, Institute of Cardiology, Warsaw, Poland.
⁵ Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
⁶ Department of Invasive Cardiology, Medical University of Bialystok, Bialystok, Poland.

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).

Materials and 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Chromosomes, Human, Pair 9 / genetics*
Female
Genetic Loci*
Humans
Linkage Disequilibrium
Male
Middle Aged
Myocardial Infarction / epidemiology
Myocardial Infarction / genetics*
Myocardial Infarction / mortality
Polymorphism, Single Nucleotide*
Proportional Hazards Models
Retrospective Studies
Survival Analysis

Grants and funding

This work was supported by National Science Center, Poland (N N 402 529139). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.