TY - JOUR
T1 - Variants of the Coagulation and Inflammation Genes Are Replicably Associated with Myocardial Infarction and Epistatically Interact in Russians
AU - Barsova, Rosa M.
AU - Lvovs, Dmitrijs
AU - Titov, Boris V.
AU - Matveeva, Natalia A.
AU - Shakhnovich, Roman M.
AU - Sukhinina, Tatiana S.
AU - Kukava, Nino G.
AU - Ruda, Mikhail Ya
AU - Karamova, Irina M.
AU - Nasibullin, Timur R.
AU - Mustafina, Olga E.
AU - Osmak, German J.
AU - Tsareva, Ekaterina Yu
AU - Kulakova, Olga G.
AU - Favorov, Sasha
AU - Favorova, Olga O.
N1 - Funding Information:
This work was supported by the Russian Foundation for Basic Research (grants 14-04-00984 to RMB, BVT, RMS, OOF and 13-04-40279-H to AVF) [http://www.rfbr.ru/rffi/eng]; by the Russian Science Foundation (grant 14-14-00605 to NAM, EYuT, OGK) [http://rscf.ru/en/]; and by National Institutes of Health (P30 CA006973 to AVF) [http:// www.nih.gov/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors are grateful to Patricia Palmer for her help with the English text of this article.
Publisher Copyright:
© 2015 Barsova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the original author and source are credited.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Background: In spite of progress in cardiovascular genetics, data on genetic background of myocardial infarction are still limited and contradictory. This applies as well to the genes involved in inflammation and coagulation processes, which play a crucial role in the disease etiopathogenesis. Methods and Results: In this study we found genetic variants of TGFB1, FGB and CRP genes associated with myocardial infarction in discovery and replication groups of Russian descent from the Moscow region and the Republic of Bashkortostan (325/185 and 220/197 samples, correspondingly). We also found and replicated biallelic combinations of TGFB1 with FGB, TGFB1 with CRP and IFNG with PTGS1 genetic variants associated with myocardial infarction providing a detectable cumulative effect.We proposed an original two-component procedure for the analysis of nonlinear (epistatic) interactions between the genes in biallelic combinations and confirmed the epistasis hypothesis for the set of alleles of IFNG with PTGS. The procedure is applicable to any pair of logical variables, e.g. carriage of two sets of alleles. The composite model that included three single gene variants and the epistatic pair has AUC of 0.66 both in discovery and replication groups. Conclusions: The genetic impact of TGFB1, FGB, CRP, IFNG, and PTGS and/or their biallelic combinations on myocardial infarction was found and replicated in Russians. Evidence of epistatic interactions between IFNG with PTGS genes was obtained both in discovery and replication groups.
AB - Background: In spite of progress in cardiovascular genetics, data on genetic background of myocardial infarction are still limited and contradictory. This applies as well to the genes involved in inflammation and coagulation processes, which play a crucial role in the disease etiopathogenesis. Methods and Results: In this study we found genetic variants of TGFB1, FGB and CRP genes associated with myocardial infarction in discovery and replication groups of Russian descent from the Moscow region and the Republic of Bashkortostan (325/185 and 220/197 samples, correspondingly). We also found and replicated biallelic combinations of TGFB1 with FGB, TGFB1 with CRP and IFNG with PTGS1 genetic variants associated with myocardial infarction providing a detectable cumulative effect.We proposed an original two-component procedure for the analysis of nonlinear (epistatic) interactions between the genes in biallelic combinations and confirmed the epistasis hypothesis for the set of alleles of IFNG with PTGS. The procedure is applicable to any pair of logical variables, e.g. carriage of two sets of alleles. The composite model that included three single gene variants and the epistatic pair has AUC of 0.66 both in discovery and replication groups. Conclusions: The genetic impact of TGFB1, FGB, CRP, IFNG, and PTGS and/or their biallelic combinations on myocardial infarction was found and replicated in Russians. Evidence of epistatic interactions between IFNG with PTGS genes was obtained both in discovery and replication groups.
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U2 - 10.1371/journal.pone.0144190
DO - 10.1371/journal.pone.0144190
M3 - Article
C2 - 26658659
AN - SCOPUS:84955567606
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 12
M1 - e0144190
ER -