PMID- 16971954
OWN - NLM
STAT- MEDLINE
DCOM- 20070221
LR  - 20061206
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 7
IP  - 8
DP  - 2006 Dec
TI  - Haplotype-specific gene expression profiles in a telomeric major 
      histocompatibility complex gene cluster and susceptibility to autoimmune 
      diseases.
PG  - 625-31
AB  - The telomeric class III region of the major histocompatibility complex is gene 
      dense, but apart from the three tumour necrosis factor (TNF) superfamily members 
      (TNF, lymphotoxin alpha and lymphotoxin beta) little is known of the expression 
      and function of the majority of the genes. Recent genetic studies in autoimmune 
      diseases, particularly rheumatoid arthritis (RA), have suggested a human 
      leukocyte antigen (HLA)-DR-independent disease effect in this region. To gain 
      further insights into these associations, we used lipopolysaccharide-stimulated 
      human macrophages to examine inducible mRNA expression and genotype-phenotype 
      relationships for genes in this region. Following stimulation in addition to the 
      expected induction of TNF mRNA, a 14-fold increase of ATP6V1G2 at 18 h (P<0.001) 
      was seen, whereas B-associated transcript (BAT)2 (P<0.001) and leucocyte-specific 
      transcript (LST)1 (P<0.001) were both downregulated. By genotyping 
      single-nucleotide polymorphisms spanning a 70 kb interval centred on the TNF 
      locus, we constructed haplotypes and determined associated expression profiles 
      for 10 genes in the cluster using quantitative real-time polymerase chain 
      reaction. Overexpression of BAT1 mRNA was associated with carriers of a haplotype 
      containing the LST1 marker transmitted to RA cases in a family study and also 
      DRB1(*)15 associated with susceptibility to nephritis in systemic lupus 
      erythematosus. The implications of our findings for the understanding of genetic 
      associations with disease susceptibility in this region are discussed.
FAU - Mewar, D
AU  - Mewar D
AD  - School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, 
      UK. d.mewar@sheffield.ac.uk
FAU - Marinou, I
AU  - Marinou I
FAU - Lee, M E
AU  - Lee ME
FAU - Timms, J M
AU  - Timms JM
FAU - Kilding, R
AU  - Kilding R
FAU - Teare, M D
AU  - Teare MD
FAU - Read, R C
AU  - Read RC
FAU - Wilson, A G
AU  - Wilson AG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060914
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (DNA Primers)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Autoimmune Diseases/*genetics
MH  - DNA Primers
MH  - *Gene Expression Profiling
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Haplotypes/genetics
MH  - Humans
MH  - Lipopolysaccharides
MH  - Major Histocompatibility Complex/*genetics
MH  - Multigene Family/*genetics
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Messenger/genetics/*metabolism
MH  - Telomere/genetics
EDAT- 2006/09/15 09:00
MHDA- 2007/02/22 09:00
CRDT- 2006/09/15 09:00
PHST- 2006/09/15 09:00 [pubmed]
PHST- 2007/02/22 09:00 [medline]
PHST- 2006/09/15 09:00 [entrez]
AID - 6364339 [pii]
AID - 10.1038/sj.gene.6364339 [doi]
PST - ppublish
SO  - Genes Immun. 2006 Dec;7(8):625-31. doi: 10.1038/sj.gene.6364339. Epub 2006 Sep 
      14.