title: Variants of the Coagulation and Inflammation Genes Are Replicably Associated with Myocardial Infarction and Epistatically Interact in Russians.
abstract: 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.
  
  
  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.
authors.affiliation: Institute of Experimental Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Barsova
authors.affiliation: Department of Computational Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Dmitrijs
authors.initials: D
authors.lastname: Lvovs
authors.affiliation: Institute of Experimental Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.|Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Titov
authors.affiliation: Institute of Experimental Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.|Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Matveeva
authors.affiliation: Department of Emergency Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.
authors.forename: Roman M
authors.initials: RM
authors.lastname: Shakhnovich
authors.affiliation: Department of Emergency Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Sukhinina
authors.affiliation: Department of Emergency Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.
authors.forename: Nino G
authors.initials: NG
authors.lastname: Kukava
authors.affiliation: Department of Emergency Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.
authors.forename: Mikhail Ya
authors.initials: MY
authors.lastname: Ruda
authors.affiliation: Division of Cardiology, Republican Cardiology Health Center, Ufa, the Republic of Bashkortostan, Russia.
authors.forename: Irina M
authors.initials: IM
authors.lastname: Karamova
authors.affiliation: Department of Genomics, Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, Russia.
authors.forename: Timur R
authors.initials: TR
authors.lastname: Nasibullin
authors.affiliation: Department of Genomics, Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, Russia.
authors.forename: Olga E
authors.initials: OE
authors.lastname: Mustafina
authors.affiliation: Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: German J
authors.initials: GJ
authors.lastname: Osmak
authors.affiliation: Institute of Experimental Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.|Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Ekaterina Yu
authors.initials: EY
authors.lastname: Tsareva
authors.affiliation: Institute of Experimental Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.|Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Olga G
authors.initials: OG
authors.lastname: Kulakova
authors.affiliation: Department of Computational Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.|Department of Oncology, Division of Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Favorov
authors.affiliation: Institute of Experimental Cardiology, Russian Cardiology Scientific and Production Center, Moscow, Russia.|Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Olga O
authors.initials: OO
authors.lastname: Favorova
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001777:Blood Coagulation / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics; D051545:Cyclooxygenase 1 / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D056726:Genetic Association Studies; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012426:Russia; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: C000592498:FGB protein, human; D005819:Genetic Markers; C573415:IFNG protein, human; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma; D005340:Fibrinogen; D002097:C-Reactive Protein; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human