Association of giant cell arteritis and polymyalgia rheumatica with different tumor necrosis factor microsatellite polymorphisms

Objective. To determine whether giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are associated with different tumor necrosis factor (TNF) microsatellite polymorphisms. Methods. Typing of TNF microsatellite polymorphisms was carried out by mole cular-based techniques on DNA obtained from a population sample of resident s from Lugo, northwestern Spain. A case-control approach was used to compar e 136 patients with GCA and/or PMR with 147 ethnically matched controls. Th e association of disease with TNF microsatellite polymorphisms was investig ated using chi-square tests and multivariate logistic regression analyses. Results. Different TNF microsatellite associations were found with GCA and PMR, In patients with isolated GCA, the primary association was with TNFa2, which was independent of the GCA associations with HLA-DRB1*0401 and *0101 . A negative association was found with TNFa10. In patients with isolated P MR, there was a positive association with TNFb3. This was found to be indep endent of the HLA-DRB1*13/*14 association in isolated PMR, TNFd4 was negati vely associated with isolated PMR. Forward stepwise logistic regression ana lyses indicated that the strongest association with GCA was provided by the TNFa2 allele, although DRB1*0401 and *0101 were still associated. PMR was primarily associated,vith TNFb3, A direct comparison of TNF allele frequenc ies between isolated GCA and isolated PMR indicated that the main differenc e between these conditions occurred in the frequency of TNFa10. Conclusion. GCA and PMR in individuals from northwestern Spain are associat ed with different TNF microsatellite polymorphisms. The primary TNF associa tions (TNFa2 and TNFb3) appear to influence susceptibility to these conditi ons independent of any HLA-DRB1 association.