Allelic combinations of immune-response genes as possible composite markers of IFN-β efficacy in multiple sclerosis patients

Olga G. Kulakova, Ekaterina Yu Tsareva, Alexey N. Boyko, Sergey G. Shchur, Evgeny I. Gusev, Dmitrijs Lvovs, Alexander V. Favorov, Koen Vandenbroeck, Olga O. Favorova

Research output: Contribution to journalArticle

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. Materials & 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. Discussion: 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. Original submitted 2 July 2012; Revision submitted 21 September 201.

Original languageEnglish (US)
Pages (from-to)1689-1700
Number of pages12
JournalPharmacogenomics
Volume13
Issue number15
DOIs
StatePublished - Nov 1 2012

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Keywords

  • APSampler
  • IFN-β
  • SNP
  • biomarker
  • composite marker
  • epistasis
  • interferon-β
  • multiple sclerosis
  • pharmacogenomics
  • polymorphism

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Kulakova, O. G., Tsareva, E. Y., Boyko, A. N., Shchur, S. G., Gusev, E. I., Lvovs, D., Favorov, A. V., Vandenbroeck, K., & Favorova, O. O. (2012). Allelic combinations of immune-response genes as possible composite markers of IFN-β efficacy in multiple sclerosis patients. Pharmacogenomics, 13(15), 1689-1700. https://doi.org/10.2217/pgs.12.161