PKP-009 Genetic polymorphisms of efectiveness to interferon-B treatment in multiple sclerosis

Abstract

BackgroundMultiple Sclerosis (MS) is the most common demyelinating disorder. Still today its pathogenesis is not well known, but there are several drugs to slow down disease progression. Interferon-B (IFN-B) drugs are useful to initiate treatment quickly after diagnosis. But treatment response to IFN-B is highly variable between individuals. There are recent investigations demonstrating genetic polymorphisms associated with the response to INF-B.PurposeTo determine the main genetic polymorphisms evaluated for possible clinical utility in MS.Material and methodsA literature review focused on genetic polymorphisms associated with IFN-B treatment responses in MS published in 2004 or later.ResultsTwenty-seven articles were reviewed. Different genes have been studied as a possible cause of inter-individual response. HLA genes have been associated with development of neutralising antibodies (NAbs) to interferon: rs4961252-GG, rs9272105-GG, HLA-DRB1*04:01, DRB1*04:08 and DRB1*16:01 polymorphisms were associated with higher risk of appearance of NAbs. In the CD46 gene the polymorphism rs2724385-AT was significantly lower and the TT genotype was higher in responders to interferon compared to non-responding patients. Other genes for pro and anti-inflammatory cytokines (IFNG, TNF, IFNB1, TGFB1) and receptors (IFNAR1, CCR5 and IL7RA) have been studied due to the inflammatory component of MS; Only the single alleles TGFB1*C and CCR5*d were associated with optimal IFN-B response. Another study associated one polymorphism (rs2542109-AA) from the ubiquitin-specific peptidase-18 gene with a better response to IFN-B. Another important gene studied was myxovirus resistance A (MXA) because previous studies demonstrated different gene expression in IFN-B patients treated. But in one study of two promoter region single nucleotide polymorphisms (rs2071430; rs17000900) no association was found with the clinical course.ConclusionAlthough individual genetic polymorphisms are relatively poor predictors, combinations of these will possibly be useful to guide therapeutic decision-making given the variety of different treatments now available with varying mechanisms of action and risks.ReferenceBaranzini SE, Madireddy LR, Cromer A, et al. Prognostic biomarkers of IFNb treatment in multiple sclerosis patients. Mult Scler 2014No conflict of interest.