Key result
Genetic variants in PCSK9, APOE, LPL, and eNOS were significantly associated with myocardial infarction, and a generalized composite model of these markers achieved an AUC of 0.676 for predicting MI risk.
Why the study?
Are genetic variants of PCSK9, APOE, LPL, MTHFR, eNOS, and the 9p21 region associated with myocardial infarction in ethnic Russians?
Case-Control (n=603)
Are genetic variants of PCSK9, APOE, LPL, MTHFR, eNOS, and the 9p21 region associated with myocardial infarction in ethnic Russians?
Odds Ratio: 1.63 (95% CI 1.16–2.3)
Absolute Event Rate: 62% vs 50%
p-value: p=0.0034
A multilocus genetic risk model incorporating variants of PCSK9, APOE, LPL, and eNOS improves the prediction of myocardial infarction risk in ethnic Russians.
Variants associated with MI in ethnic Russians may aid risk prediction; leaves open clinical utility pending prospective validation.
In search of genetic markers of myocardial infarction (MI) risk, which have prognostic significance for Russians, we performed a replication study of MI association with genetic variants of PCSK9 (rs562556), APOE (epsilon polymorphism, rs7412 and rs429358), LPL (rs320), MTHFR (rs1801133), eNOS (rs2070744), and the 9p21 region (rs1333049) in 405 patients with MI and 198 controls. Significant MI association was observed with variants of the lipid metabolism genes (PCSK9, APOE and LPL), and of eNOS. The SNPs in the MTHFR gene and the 9p21 region were not significantly associated with MI one by one but were included in several different MI-associated allelic combinations identified by multilocus analysis. Since we have not revealed nonlinear epistatic interactions between the components of the identified combinations, we postulate that the cumulative effect of genes that form a combination arises from the summation of their small independent contributions. The prognostic significance of the additive composite model built from the PCSK9, APOE, LPL, and eNOS genes as genetic markers was assessed using ROC analysis. After we included these markers in the previously published composite model of individual genetic risk of MI, the prognostic efficacy in our sample reached AUC = 0.676. However, the results obtained in this study certainly need to be replicated in an independent sample of Russians.
No takes yet. Share an insight, caveat, or question.
Kukava et al. (2017) conducted a case-control in Myocardial infarction (n=603). Genetic variants in PCSK9, APOE, LPL, MTHFR, eNOS, and 9p21 vs. Healthy controls was evaluated on Myocardial infarction (associated with eNOS* C allele carriage) (OR 1.63, 95% CI 1.16-2.30, p=0.0034). Genetic variants in PCSK9, APOE, LPL, and eNOS were significantly associated with myocardial infarction, and a generalized composite model of these markers achieved an AUC of 0.676 for predicting MI risk.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: