Source:http://linkedlifedata.com/resource/pubmed/id/18178846
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2008-1-7
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pubmed:abstractText |
TCRzeta (CD247) functions as an amplification module in the TCR signaling cascade and is essential for assembly and surface expression of the TCR/CD3 complex. The TCRzeta-chain is down-regulated in many chronic infectious and inflammatory diseases, including systemic lupus erythematosus (SLE). It is unclear whether reduced TCRzeta expression is a cause or a consequence of chronic inflammatory responses. We have addressed this question by adopting a combined genetic and functional approach. We analyzed TCRzeta protein expression using a FACS-based expression index and documented considerable, but longitudinally stable, variation in TCRzeta expression in healthy individuals. The variation in TCRzeta expression was associated with polymorphisms in the CD3Z 3'-untranslated region (UTR) in SLE patients and healthy controls. Detailed mapping of the 3'-UTR revealed that the minor alleles of two single nucleotide polymorphisms (SNPs) in strong disequilibrium (rs1052230 and rs1052231) were the causal variants associated with low TCRzeta expression (p=0.015). Using allelic imbalance analysis, the minor alleles of these 3'-UTR SNPs were associated with one-third of the level of mRNA compared with the major allele. A family-based association analysis showed that the haplotype carrying the low-expression variants predisposes to SLE (p=0.033). This suggests that a genetically determined reduction in TCRzeta expression has functional consequences manifested by systemic autoimmunity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/CD3 antigen, zeta chain,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/antigen T cell receptor, zeta chain
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
180
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1060-70
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pubmed:meshHeading |
pubmed-meshheading:18178846-3' Untranslated Regions,
pubmed-meshheading:18178846-Adolescent,
pubmed-meshheading:18178846-Adult,
pubmed-meshheading:18178846-Allelic Imbalance,
pubmed-meshheading:18178846-Antigens, CD3,
pubmed-meshheading:18178846-Autoimmunity,
pubmed-meshheading:18178846-Base Sequence,
pubmed-meshheading:18178846-Female,
pubmed-meshheading:18178846-Haplotypes,
pubmed-meshheading:18178846-Humans,
pubmed-meshheading:18178846-Lupus Erythematosus, Systemic,
pubmed-meshheading:18178846-Male,
pubmed-meshheading:18178846-Membrane Proteins,
pubmed-meshheading:18178846-Middle Aged,
pubmed-meshheading:18178846-Polymorphism, Single Nucleotide,
pubmed-meshheading:18178846-RNA, Messenger,
pubmed-meshheading:18178846-Receptors, Antigen, T-Cell
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pubmed:year |
2008
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pubmed:articleTitle |
Polymorphisms in the CD3Z gene influence TCRzeta expression in systemic lupus erythematosus patients and healthy controls.
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pubmed:affiliation |
Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, UK. c.gorman@imperial.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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