| IFN-beta pharmacogenomics in multiple sclerosis. | |
| | |
MedLine Citation:
|
PMID: 20712530 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Koen Vandenbroeck; Elena Urcelay; Manuel Comabella |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
|
Title: Pharmacogenomics Volume: 11 ISSN: 1744-8042 ISO Abbreviation: Pharmacogenomics Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-08-17 Completed Date: 2010-12-28 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100897350 Medline TA: Pharmacogenomics Country: England |
Other Details:
|
Languages: eng Pagination: 1137-48 Citation Subset: IM |
Affiliation:
|
Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain. k.vandenbroeck@ikerbasque.org |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Gene Expression Profiling Glypicans / genetics Humans Interferon Type I / genetics Interferon Type I, Recombinant / therapeutic use* Multiple Sclerosis* / drug therapy, genetics Pharmacogenetics* Polymorphism, Single Nucleotide |
| Chemical | |
Reg. No./Substance:
|
0/GPC5 protein, human; 0/Glypicans; 0/Interferon Type I; 0/Interferon Type I, Recombinant |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Tailored therapy of ACE inhibitors in stable coronary artery disease: pharmacogenetic profiling of t...
Next Document: Realities and expectations of pharmacogenomics and personalized medicine: impact of translating gene...