Genetic analysis of the 3′ untranslated region of the tumour necrosis factor shows a highly conserved region in rheumatoid arthritis affected and unaffected subjects
- aDepartment of Microbiology, National University of Ireland Cork, Cork, Ireland, bDepartment of Medicine and Rheumatology, Cork University Hospital, Cork, Ireland
- Professor O’Gara.
- Received 5 May 1998
- Revised 30 July 1998
Abstract
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.
