Linked Life Data

20712530

Source:http://linkedlifedata.com/resource/pubmed/id/20712530

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-8-17
pubmed:abstractText
Multiple sclerosis (MS) is a condition of the CNS marked by inflammation and neurodegeneration. Interferon (IFN)-beta was the first, and still is the main, immunomodulatory treatment for MS. Its clinical efficacy is limited, and a proportion of patients, ranging between 20-55%, do not respond to the therapy. Identification and subsequently, implementation in the clinic of biomarkers predictive for individual therapeutic response would facilitate improved patient care in addition to ensuring a more rational provision of this therapy. In this article, we summarize the main findings from studies addressing the pharmacogenomics of clinical response to IFN-beta in MS by either whole-genome association scans, candidate gene or transcriptomics studies. Whole-genome DNA association screens have revealed a high representation of brain-specific genes, and have hinted toward both extracellular ligand-gated ion channels and type I IFNs pathway genes as important categories of genetic IFN-beta response modifiers. One hit, glypican 5 (GPC5), was recently replicated in an independent study of IFN-beta responsiveness. Recent RNA transcriptomics studies have revealed the occurrence of a pre-existing type I IFN gene-expression signature, composed of genes that are predominantly induced by type I IFNs, as a potential contributing feature of poor response to therapy. Thus, while the outlines of a complex polygenic mechanism are gradually being uncovered, the main challenges for the near future will reside in the robust validation of identified response-modifying genes as well as in the decipherment of the mechanistic relationships between these genes and clinical response to IFN-beta.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1744-8042
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1137-48
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
IFN-beta pharmacogenomics in multiple sclerosis.
pubmed:affiliation
Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain. k.vandenbroeck@ikerbasque.org
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't