TNF NCO-I RFLP IS NOT AN INDEPENDENT RISK FACTOR IN RHEUMATOID-ARTHRITIS

The human TNF genes are located within the MHC class-III region on chr omosome 6. The presence or absence of an Nco-I restriction site in the 5' non-coding sequence of the TNF beta gene defines two alleles (TNFB 1 and TNFB*2). The segregation of these alleles has been associated w ith levels of TNF alpha or TNF beta production in systemic lupus eryth ematosis (SLE), insulin-dependent diabetes mellitus (IDDM) and in heal thy control individuals. Rheumatoid arthritis (RA) is characterized by high levels of TNF alpha within the synovial fluid and to address the question of whether this could be brought about by a genetic predispo sition to high TNF production by RA individuals, we examined the distr ibution of this Nco-I polymorphism in 98 healthy volunteers and 123 pa tients with active rheumatoid arthritis.-No difference was observed be tween the normal and RA groups with respect to haplotype segregation o r allelic frequency. Furthermore, no difference was observed between D R4(+) or DR4(-) individuals in the control or RA groups. These data de monstrate that the high level of TNF alpha seen in the joints of RA pa tients is unlikely to be due to a genetic predisposition of these pati ents to high TNF alpha production, as defined by the TNF Nco-I restric tion fragment length polymorphism (RFLP).