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.
BACKGROUND: IFN-β is widely used as the first-line disease-modifying treatment for multiple sclerosis. However, 30-50% of multiple sclerosispatients 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 sclerosispatients 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.
Authors: Valery I Turobov; Alexey V Danilkovich; Alexei B Shevelev; Yulia K Biryukova; Natalia V Pozdniakova; Viatcheslav N Azev; Arkady N Murashev; Valery M Lipkin; Igor P Udovichenko Journal: Front Pharmacol Date: 2018-02-23 Impact factor: 5.810