Single-Nucleotide Polymorphisms in Response to Interferon-Beta Therapy in Multiple Sclerosis.
Summary of "Single-Nucleotide Polymorphisms in Response to Interferon-Beta Therapy in Multiple Sclerosis."
Interferon-beta (IFN-β) is one of the main first-line disease-modifying drugs indicated for the treatment of multiple sclerosis (MS). The drug exhibits only limited effectiveness, and does not produce clinical benefits in around 20%-50% of patients. The availability of biomarkers would be beneficial for identification of patients at high risk of treatment failure, before initiation of therapy. Over the last 5 years, the search for such biomarkers has intensified and various promising candidates have been uncovered. Here, we review the main attempts undertaken to identify polymorphic variants associated with response to IFN-β therapy in MS by means of candidate gene approaches and whole-genome association scans. Despite substantial progress made in the field, there is still a long way to go before biomarker discoveries can be incorporated into clinical practice to predict IFN-β-responder status in MS patients.
1 Neurogenomiks Group, Universidad del País Vasco (UPV/EHU) , Leioa, Spain .
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20836710
- DOI: http://dx.doi.org/10.1089/jir.2010.0085
Medical and Biotech [MESH] Definitions
Interferon Type I
Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).
Receptor, Interferon Alpha-beta
A ubiquitously expressed heterodimeric receptor that is specific for both INTERFERON-ALPHA and INTERFERON-BETA. It is composed of two subunits referred to as IFNAR1 and IFNAR2. The IFNAR2 subunit is believed to serve as the ligand-binding chain; however both chains are required for signal transduction. The interferon alpha-beta receptor signals through the action of JANUS KINASES such as the TYK2 KINASE.
Interferon Regulatory Factors
A family of transcription factors that share an N-terminal HELIX-TURN-HELIX MOTIF and bind INTERFERON-inducible promoters to control GENE expression. IRF proteins bind specific DNA sequences such as interferon-stimulated response elements, interferon regulatory elements, and the interferon consensus sequence.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
Interferon Regulatory Factor-1
An interferon regulatory factor that binds upstream TRANSCRIPTIONAL REGULATORY ELEMENTS in the GENES for INTERFERON-ALPHA and INTERFERON-BETA. It functions as a transcriptional activator for the INTERFERON TYPE I genes.
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