title: Allelic combinations of immune-response genes as possible composite markers of IFN-β efficacy in multiple sclerosis patients.
abstract: BACKGROUND
  IFN-β is widely used as the first-line disease-modifying treatment for multiple sclerosis. However, 30-50% of multiple sclerosis patients do not respond to this therapy. Identification of genetic variants and their combinations that predict responsiveness to IFN-β could be useful for treatment prognosis.
  
  
  METHODS
  The combinations of alleles of nine polymorphic loci in immune-response genes were analyzed in 253 Russian multiple sclerosis patients as possible determinants of clinically optimal IFN-β treatment response using APSampler software.
  
  
  RESULTS
  Carriage of TGFB1*-509C and CCR5*d was associated with favorable IFN-β response by itself. CCR5*d, IFNAR1*16725G, IFNG*874T and IFNB1*153T/T were the components of the combinations, associated with clinically optimal response to IFN-β. Carriage of composite markers (CCR5*d + IFNAR1*G + IFNB1*T/T) or (CCR5*d + IFNAR1*G + IFNG*T) is beneficial for IFN-β treatment efficacy.
  
  
  CONCLUSIONS
  The data obtained provides evidence of the cumulative effect of immune-response genes on IFN-β treatment efficacy. This joint contribution may reflect the additive effect of independent allelic variants and epistatic interactions between some of them.
authors.affiliation: N.I. Pirogov Russian National Research Medical University, Moscow, Russia. olga.koulakova@gmail.com
authors.forename: Olga G
authors.initials: OG
authors.lastname: Kulakova
authors.forename: Ekaterina Yu
authors.initials: EY
authors.lastname: Tsareva
authors.forename: Alexey N
authors.initials: AN
authors.lastname: Boyko
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Shchur
authors.forename: Evgeny I
authors.initials: EI
authors.lastname: Gusev
authors.forename: Dmitrijs
authors.initials: D
authors.lastname: Lvovs
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Favorov
authors.forename: Koen
authors.initials: K
authors.lastname: Vandenbroeck
authors.forename: Olga O
authors.initials: OO
authors.lastname: Favorova
mesh_terms: D000483:Alleles; D005787:Gene Frequency / Q000276:immunology; D056426:Genetic Loci / Q000276:immunology; D005838:Genotype; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology
chemical_list: C507964:IFNAR1 protein, human; D019713:Receptors, CCR5; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta