Multilocus analysis of genetic susceptibility to myocardial infarction in Russians: Replication study

N. G. Kukava, B. V. Titov, G. J. Osmak, N. A. Matveeva, O. G. Kulakova, Alexander Favorov, R. M. Shakhnovich, M. Ya Ruda, O. O. Favorova

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)74-83
Number of pages10
JournalActa Naturae
Volume9
Issue number4
StatePublished - Jan 1 2017

Fingerprint

Genetic Predisposition to Disease
Genes
Myocardial Infarction
Genetic Markers
Composite materials
Polymorphism
Genetic Models
Lipid Metabolism
ROC Curve
Area Under Curve
Single Nucleotide Polymorphism

Keywords

  • Allelic polymorphism
  • Genes
  • Genetic markers
  • Multilocus analysis
  • Myocardial infarction
  • Russians

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Kukava, N. G., Titov, B. V., Osmak, G. J., Matveeva, N. A., Kulakova, O. G., Favorov, A., ... Favorova, O. O. (2017). Multilocus analysis of genetic susceptibility to myocardial infarction in Russians: Replication study. Acta Naturae, 9(4), 74-83.

Multilocus analysis of genetic susceptibility to myocardial infarction in Russians : Replication study. / Kukava, N. G.; Titov, B. V.; Osmak, G. J.; Matveeva, N. A.; Kulakova, O. G.; Favorov, Alexander; Shakhnovich, R. M.; Ruda, M. Ya; Favorova, O. O.

In: Acta Naturae, Vol. 9, No. 4, 01.01.2017, p. 74-83.

Research output: Contribution to journalArticle

Kukava, NG, Titov, BV, Osmak, GJ, Matveeva, NA, Kulakova, OG, Favorov, A, Shakhnovich, RM, Ruda, MY & Favorova, OO 2017, 'Multilocus analysis of genetic susceptibility to myocardial infarction in Russians: Replication study', Acta Naturae, vol. 9, no. 4, pp. 74-83.
Kukava NG, Titov BV, Osmak GJ, Matveeva NA, Kulakova OG, Favorov A et al. Multilocus analysis of genetic susceptibility to myocardial infarction in Russians: Replication study. Acta Naturae. 2017 Jan 1;9(4):74-83.
Kukava, N. G. ; Titov, B. V. ; Osmak, G. J. ; Matveeva, N. A. ; Kulakova, O. G. ; Favorov, Alexander ; Shakhnovich, R. M. ; Ruda, M. Ya ; Favorova, O. O. / Multilocus analysis of genetic susceptibility to myocardial infarction in Russians : Replication study. In: Acta Naturae. 2017 ; Vol. 9, No. 4. pp. 74-83.
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