PMID- 16075257
OWN - NLM
STAT- MEDLINE
DCOM- 20060327
LR  - 20181113
IS  - 0946-2716 (Print)
IS  - 0946-2716 (Linking)
VI  - 83
IP  - 10
DP  - 2005 Oct
TI  - Gene expression and genotyping studies implicate the interleukin 7 receptor in 
      the pathogenesis of primary progressive multiple sclerosis.
PG  - 822-30
AB  - 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.
FAU - Booth, D R
AU  - Booth DR
AD  - Institute for Immunology and Allergy Research, Westmead Millennium Institute, 
      University of Sydney, Australia. davidb@westgate.wh.usyd.edu.au
FAU - Arthur, A T
AU  - Arthur AT
FAU - Teutsch, S M
AU  - Teutsch SM
FAU - Bye, C
AU  - Bye C
FAU - Rubio, J
AU  - Rubio J
FAU - Armati, P J
AU  - Armati PJ
FAU - Pollard, J D
AU  - Pollard JD
FAU - Heard, R N S
AU  - Heard RN
FAU - Stewart, G J
AU  - Stewart GJ
CN  - Southern MS Genetics Consortium
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050802
PL  - Germany
TA  - J Mol Med (Berl)
JT  - Journal of molecular medicine (Berlin, Germany)
JID - 9504370
RN  - 0 (Receptors, Interleukin-7)
SB  - IM
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression
MH  - *Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Genotype
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Multiple Sclerosis/*genetics
MH  - Receptors, Interleukin-7/*genetics
EDAT- 2005/08/03 09:00
MHDA- 2006/03/28 09:00
CRDT- 2005/08/03 09:00
PHST- 2004/12/08 00:00 [received]
PHST- 2005/05/03 00:00 [accepted]
PHST- 2005/08/03 09:00 [pubmed]
PHST- 2006/03/28 09:00 [medline]
PHST- 2005/08/03 09:00 [entrez]
AID - 10.1007/s00109-005-0684-y [doi]
PST - ppublish
SO  - J Mol Med (Berl). 2005 Oct;83(10):822-30. doi: 10.1007/s00109-005-0684-y. Epub 
      2005 Aug 2.