Linked Life Data

16075257

Source:http://linkedlifedata.com/resource/pubmed/id/16075257

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2005-10-6
pubmed:abstractText
Multiple sclerosis (MS) is an enigmatic disease of the central nervous system resulting in sclerotic plaques with the pathological hallmarks of demyelination and axonal damage, which can be directly or indirectly orchestrated by cells from the peripheral circulation. The majority of patients with MS follow a relapsing-remitting course in the early stages of the disease (RRMS) but most ultimately enter a secondary progressive phase (SPMS). About 10% of patients follow a primary progressive course from the onset (PPMS). We measured gene expression in whole blood of people with and without chronic progressive MS (CPMS), PPMS and SPMS, to discover genes which may be differentially expressed in peripheral blood in active disease, and so identify pathologically significant genes and pathways; and we investigated genetic differences in the promoters of dysregulated genes encoded in genomic regions associated with MS. If SPMS and PPMS were independently compared to the controls, there was little overlap in the set of most dysregulated genes. Ribosomal protein genes, whose expression is usually associated with cell proliferation and activation, were dramatically over-represented in the set of most down-regulated genes in PPMS compared to SPMS (P < 10(-4), chi(2)). The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. One interleukin 7 receptor (IL7R) promoter single nucleotide polymorphism (SNP), -504 C, was undertransmitted in PPMS trios (P = 0.05, TDT), and carriers of this allele were under-represented in PPMS cases from two independent patient cohorts (combined P = 0.006, FE). The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P < 0.01, t test). These data support the hypothesis that PPMS has significant pathogenetic differences from SPMS, and that IL7R may be a useful therapeutic target in PPMS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0946-2716
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
822-30
pubmed:dateRevised
2011-7-8
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis.
pubmed:affiliation
Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Australia. davidb@westgate.wh.usyd.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't