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

Szpakowicz A, Kiliszek M, Pepinski W, Waszkiewicz E, Franaszczyk M, Skawronska M, Ploski R, Niemcunowicz-Janica A, Dobrzycki S, Opolski G, Musial WJ, Kaminski KA - PLoS ONE (2014)

Bottom Line: 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 genotypes associated with higher risk for ACS show a protective effect in terms of further survival (instead of a deteriorating prognosis, as reported previously).

View Article: PubMed Central - PubMed

Affiliation: Department of 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.

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The rs10757278 polymorphism and long-term survival - subgroup of high-risk patients (GRACE risk score ≥155) from the derivation group.GG high-risk homozygotes had significantly higher probability of survival compared to other genotypes (p = 0.032 after adjustment for Bonferroni correction, log-rank test).
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pone-0104635-g002: The rs10757278 polymorphism and long-term survival - subgroup of high-risk patients (GRACE risk score ≥155) from the derivation group.GG high-risk homozygotes had significantly higher probability of survival compared to other genotypes (p = 0.032 after adjustment for Bonferroni correction, log-rank test).

Mentions: However, in the subgroup of high-risk patients (GRACE risk score ≥155, n = 238, 26.9% mortality [n = 64]), visual analysis of survival curves showed strikingly better survival of GG high-risk homozygotes compared to both other genotypes. The curves for heterozygotes and low-risk homozygotes had an almost similar course and were therefore collapsed together for further analysis. Kaplan-Meier surviving curves for the subgroup of high-risk patients and rs10757278 polymorphism are shown in figure 2. The difference was statistically significant (p = 0.032 after adjustment for Bonferroni correction, log-rank test). Mortality rates for specific genotypes in the subgroup of high-risk patients are shown in table 1.


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

Szpakowicz A, Kiliszek M, Pepinski W, Waszkiewicz E, Franaszczyk M, Skawronska M, Ploski R, Niemcunowicz-Janica A, Dobrzycki S, Opolski G, Musial WJ, Kaminski KA - PLoS ONE (2014)

The rs10757278 polymorphism and long-term survival - subgroup of high-risk patients (GRACE risk score ≥155) from the derivation group.GG high-risk homozygotes had significantly higher probability of survival compared to other genotypes (p = 0.032 after adjustment for Bonferroni correction, log-rank test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126747&req=5

pone-0104635-g002: The rs10757278 polymorphism and long-term survival - subgroup of high-risk patients (GRACE risk score ≥155) from the derivation group.GG high-risk homozygotes had significantly higher probability of survival compared to other genotypes (p = 0.032 after adjustment for Bonferroni correction, log-rank test).
Mentions: However, in the subgroup of high-risk patients (GRACE risk score ≥155, n = 238, 26.9% mortality [n = 64]), visual analysis of survival curves showed strikingly better survival of GG high-risk homozygotes compared to both other genotypes. The curves for heterozygotes and low-risk homozygotes had an almost similar course and were therefore collapsed together for further analysis. Kaplan-Meier surviving curves for the subgroup of high-risk patients and rs10757278 polymorphism are shown in figure 2. The difference was statistically significant (p = 0.032 after adjustment for Bonferroni correction, log-rank test). Mortality rates for specific genotypes in the subgroup of high-risk patients are shown in table 1.

Bottom Line: 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 genotypes associated with higher risk for ACS show a protective effect in terms of further survival (instead of a deteriorating prognosis, as reported previously).

View Article: PubMed Central - PubMed

Affiliation: Department of 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.

Show MeSH
Related in: MedlinePlus