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a Department of
Microbiology, National University of Ireland Cork, Cork, Ireland, b Department of Medicine and Rheumatology, Cork
University Hospital, Cork, Ireland
Correspondence to: Professor O'Gara.
Received 5 May 1998;
Revised version accepted for publication 30 July
1998
Tumour necrosis factor (TNF) is a key proinflammatory mediator
in rheumatoid arthritis (RA). The TNF locus, situated in the class III
region of the MHC, is flanked by five microsatellite markers. It has
previously been shown that this region influences susceptibility to RA;
two TNF microsatellite haplotypes were found to be associated with RA.
Evidence from murine studies has indicated that variation in the TNF 3'
untranslated region (UTR) could be associated with altered regulation
of TNF biosynthesis.
In order to identify possible RA associated polymorphisms, more
than 800 bp of the TNF 3' UTR was genetically analysed in RA affected
and unaffected subjects possessing specific RA and non-RA associated
TNF microsatellite haplotypes. The TNF 3' UTR region was analysed using
two mutation detection methods, PCR-SSCP and NIRCA analysis and DNA sequencing.
No genetic differences were observed in the human TNF 3' UTR between
subjects, that is, irrespective of RA status or TNF haplotype, and also
compared with previously published TNF sequences from human sources.
Therefore it can be concluded that the TNF 3' UTR in this population
was highly conserved and did not influence susceptibility to RA.
This article has been cited by other articles:
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  A. Amcheslavsky, W. Zou, and Z. Bar-Shavit Toll-like Receptor 9 Regulates Tumor Necrosis Factor-{alpha} Expression by Different Mechanisms: IMPLICATIONS FOR OSTEOCLASTOGENESIS J. Biol. Chem., December 24, 2004; 279(52): 54039 - 54045. [Abstract] [Full Text] [PDF]
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