Polymorphism of 9p21.3 Locus Is Associated with 5-Year Survival in High-Risk Patients with Myocardial Infarction

Abstract

ObjectiveThe 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 methodsWe 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.ResultsThe 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).ConclusionsThe 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.

Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility

“…They found that 9p21.3 locus is associated with five-year survival in high-risk patients with myocardial infarction [20]. Zeng et al investigated whether rs10757278 was associated with acute coronary syndrome (ACS) in a Chinese Han population [21].…”

“…Szpakowicz et al performed a retrospective analysis of data collected prospectively in two independent registries of consecutive patients to investigate the association of the 9p21.3 locus (rs10757278, rs1333049 and rs4977574 polymorphisms) with five-year overall mortality in patients with ST-elevation myocardial infarction [ 20 ]. They found that 9p21.3 locus is associated with five-year survival in high-risk patients with myocardial infarction [ 20 ]. Zeng et al investigated whether rs10757278 was associated with acute coronary syndrome (ACS) in a Chinese Han population [ 21 ].…”

Genetic predictors of five-year outcomes of acute coronary syndrome

“…Однако тенденция в виде меньшей доли носителей генотипа АА в подгруппах с неблагоприятными сердечно-сосудистыми исходами -сохраняются. Полученные данные о протективном эффекте rs10757278 в отношении риска развития сердечно-сосудистых осложнений ОКС в течение пятилетнего наблюдения соотносятся с результатами зарубежных исследований [13].…”

Clinical Significance of Coronary Artery Disease Genetic Markers: Reality or Far Future?

“…В частности, была продемонстрирована строгая связь генетических пре-дикторов с отдаленными исходами у наиболее тяже-лых больных ИМ -имевших многососудистое пора-жение КА или стратифицированных по шкале GRACE [16,17].…”