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Genetic risk factors for myocardial infarction more clearly manifest for early age of first onset

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Abstract

Epidemiological genetics established that heritability in determining the risk of myocardial infarction (MI) is substantially greater when MI occurs early in life. However, the genetic architecture of early-onset and late-onset MI was not compared. We analyzed genotype frequencies of SNPs in/near 20 genes whose protein products are involved in the pathogenesis of atherosclerosis in two groups of Russian patients with MI: the first group included patients with age of first MI onset <60 years (N = 230) and the second group with onset ≥60 years (N = 174). The control group of corresponding ethnicity consisted of 193 unrelated volunteers without cardiovascular diseases (93 individuals were over 60 years). We found that in the group of patients with age of onset <60 years, SNPs FGB rs1800788*T, TGFB1 rs1982073*T/T, ENOS rs2070744*C and CRP rs1130864*T/T were associated with risk of MI, whereas in patients with age of onset ≥60 years, only TGFB1 rs1982073*T/T was associated with risk of MI. Using APSampler software, we found composite markers associated with MI only in patients with early onset: FGB rs1800788*T + TGFB1 rs1982073*T; FGB rs1800788*T + LPL rs328*C + IL4 rs2243250*C; FGB rs1800788*T + ENOS rs2070744*C (Fisher p values of 1.4 × 10−6 to 2.2 × 10−5; the permutation p values of 1.1 × 10−5 to 3.0 × 10−4; ORs = 2.67–2.54). Alleles included in the combinations were associated with MI less significantly and with lower ORs than the combinations themselves. The result showed a substantially greater contribution of the genetic component in the development of MI if it occurs early in life, and demonstrated the usefulness of genetic testing for young people.

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Acknowledgements

This work was supported by the Russian Science Foundation (Project 16-14-10251). Authors are grateful to Patricia Palmer for her help with the English text of this article.

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Authors and Affiliations

  1. Institute of Experimental Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia

    Boris V. Titov, German J. Osmak, Natalia A. Matveeva, Nino G. Kukava & Olga O. Favorova

  2. Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Moscow, Russia

    Boris V. Titov, German J. Osmak, Natalia A. Matveeva & Olga O. Favorova

  3. Department of Emergency Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia

    Nino G. Kukava, Roman M. Shakhnovich & Mikhail Ya. Ruda

  4. Department of Computational Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia

    Alexander V. Favorov

  5. Department of Oncology, Division of Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Alexander V. Favorov

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  1. Boris V. Titov
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Titov, B.V., Osmak, G.J., Matveeva, N.A. et al. Genetic risk factors for myocardial infarction more clearly manifest for early age of first onset. Mol Biol Rep 44, 315–321 (2017). https://doi.org/10.1007/s11033-017-4112-5

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