Genetic analysis of the 3 ' untranslated region of the tumour necrosis factor shows a highly conserved region in rheumatoid arthritis affected and unaffected subjects

Tumour necrosis factor (TNF) is a key proinflammatory mediator in rheumatoi d arthritis (RA). The TNF locus, situated in the class III region of the MH C, is flanked by five microsatellite markers. It has previously been shown that this region influences susceptibility to RA; two TNF microsatellite ha plotypes 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 s ubjects possessing specific RA and non-RA associated TNF microsatellite hap lotypes. The TNF 3' UTR region was analysed using two mutation detection me thods, PCR-SSCP and NIRCA analysis and DNA sequencing. No genetic differences were observed in the human TNF 3' UTR between subjec ts, that is, irrespective of RA status or TNF haplotype, and also compared with previously published TNF sequences from human sources. Therefore it ca n be concluded that the TNF 3' UTR in this population was highly conserved and did not influence susceptibility to RA.