Dominika Maciorkowska

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

Objective The rs1333049, rs10757278 and rs4977574 are single nucleotide polymorphisms (SNPs) of chromosome 9p21 locus that are associated with prevalence of acute coronary syndromes (ACS). The rs1333049 SNP was also associated with cardiac outcome 6 months post ACS. No data concerning their association with long term prognosis after myocardial infarction is available. 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) treated invasively. Materials and Methods We performed a retrospective analysis of data collected prospectively in a registry of consecutive patients with STEMI treated with primary PCI. Genotyping was performed with a TaqMan method. The analyzed end-point was total 5-year mortality. Results The study group comprised 589 patients: 25.3% of females (n = 149), mean age 62.4±11.9 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), low-risk homozygotes had significantly better 5-year survival compared to other genotypes. The hazard ratio associated with high-risk genotype (high-risk homozygote or heterozygote) was: HR = 2.9 (95%CI 1.4–6.1) for the rs4977574 polymorphism, HR = 2.6 (1.25–5.3) for the rs1333049 one and HR = 2.35 (1.2–4.6) for the rs10757278 one (Cox proportional hazards model). Conclusions The 9p21.3 locus is associated with 5-year mortality in high-risk patients with STEMI. This finding, due to very high effect size, could potentially be applied into clinical practice, if appropriate methods are elaborated.

The rs1801133 polymorphism of methylenetetrahydrofolate reductase gene- the association with 5-year survival in patients with ST-elevation myocardial infarction.

PURPOSE Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in endothelial nitric oxide synthase (eNOS) coupling and homocysteine metabolism. The rs1801133 polymorphism of the MTHFR gene affects risk of coronary artery disease. We assessed its influence on 5-year survival of patients with ST-elevation acute myocardial infarction (STEMI). MATERIAL/METHODS The study group comprised consecutive patients with STEMI. Genotyping was performed with a TaqMan SNP Genotyping Assay using the ABI 7500 Real Time PCR System (Applied Biosystems). The analyzed end-point was all-cause 5-year survival. RESULTS The study group comprised 637 patients (mean age 62.3 ± 11.9 years; 25.1% females, n=160; 5-year mortality 16.3%, n=104). The percentages of TT, CT and CC genotypes were: 10.8 (n=69), 39.7 (n=253) and 49.45 (n=315), respectively. No significant differences in clinical characteristics were identified between the genotypes (p>0.05 for all parameters). Eleven (15.9%) TT homozygotes, 40 (15.8%) heterozygotes and 53 (16.8%) CC homozygotes died during follow up (p=0.99 log-rank test). TT homozygotes presented only weak and insignificant tendency towards higher mortality rates in subgroups of patients ≤75 years old (15.6 vs. 11.54%, p=0.35) or with intermediate risk according to the GRACE risk score (13.3% vs. 8.76%, p=0.42). CONCLUSIONS The rs1801133 polymorphism did not show significant association with 5-year survival.