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

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.