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

作者：Kulakova Olga G^*; Tsareva Ekaterina Yu; Boyko Alexey N; Shchur Sergey G; Gusev Evgeny I; Lvovs Dmitrijs; Favorov Alexander V; Vandenbroeck Koen; Favorova Olga O

来源：Pharmacogenomics, 2012, 13(15): 1689-1700.

DOI：10.2217/PGS.12.161

• APSampler
• biomarker
• composite marker
• epistasis
• UFB-beta
• interferon-beta
• multiple sclerosis
• pharmacogenomics
• polymorphism
• SNP

Background: IFN-beta 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-beta could be useful for treatment prognosis. Materials %26 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-beta treatment response using APSampler software. Results: Carriage of TGFB1*-509C and CCR5*d was associated with favorable IFN-beta 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-beta. Carriage of composite markers (CCR5*d + IFNAR1*G + IFNB1*T/T) or (CCR5*d + IFNAR1*G + IFNG*T) is beneficial for IFN-beta treatment efficacy. Discussion: The data obtained provides evidence of the cumulative effect of immune-response genes on IFN-beta treatment efficacy. This joint contribution may reflect the additive effect of independent allelic variants and epistatic interactions between some of them.

• 出版日期2012-11