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Multilocus Analysis of Genetic Susceptibility to Myocardial Infarction in Russians: Replication Study.

N G Kukava1, B V Titov1,2, G J Osmak1,2

  • 1National Medical Scientific Center for Cardiology, 3rd Cherepkovskaya Str. 15a, Moscow, 121552 , Russia.

Acta Naturae
|January 18, 2018
PubMed
Summary

Researchers identified genetic markers for myocardial infarction (MI) risk in Russians. Key lipid metabolism and eNOS gene variants, along with MTHFR and 9p21 regions, showed significant associations, improving prognostic models.

Keywords:
Russiansallelic polymorphismgenesgenetic markersmultilocus analysismyocardial infarction

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Area of Science:

  • Genetics and Cardiovascular Disease Epidemiology
  • Molecular Biology and Disease Mechanisms

Background:

  • Identifying genetic markers for myocardial infarction (MI) risk is crucial for personalized medicine.
  • Previous studies suggest associations between various genetic variants and MI, but replication in diverse populations is needed.
  • Understanding the genetic architecture of MI in the Russian population can improve risk prediction.

Purpose of the Study:

  • To replicate the association of specific genetic variants with MI risk in a Russian cohort.
  • To investigate the prognostic significance of identified genetic markers using a composite model.
  • To explore potential gene-gene interactions (epistasis) influencing MI risk.

Main Methods:

  • A case-control study involving 405 MI patients and 198 controls from the Russian population.
  • Genotyping of single nucleotide polymorphisms (SNPs) in PCSK9, APOE, LPL, MTHFR, eNOS, and the 9p21 region.
  • Multilocus analysis to identify associated allelic combinations and ROC analysis to assess prognostic efficacy of a composite model.

Main Results:

  • Significant associations with MI were found for variants in lipid metabolism genes (PCSK9, APOE, LPL) and the eNOS gene.
  • SNPs in MTHFR and the 9p21 region were not individually significant but formed MI-associated combinations via multilocus analysis.
  • An additive composite model incorporating PCSK9, APOE, LPL, and eNOS demonstrated prognostic utility (AUC = 0.676) when added to a prior risk model.

Conclusions:

  • Genetic variants in PCSK9, APOE, LPL, and eNOS are associated with MI risk in the Russian population.
  • The cumulative effect of multiple genetic variants, rather than strong individual gene-gene interactions, likely contributes to MI risk.
  • The developed composite genetic risk model shows potential for improving MI prognosis, warranting replication in independent Russian cohorts.