Influence of HLA-DRB1 and TNF microsatellite polymorphisms on the expression of extraarticular manifestations in rheumatoid arthritis patients from northwest Spain

Objective. To determine whether extraarticular manifestations (EAM) in rheumatoid arthritis (RA) patients from northwest (NW) Spain are associated with particular HLA-DRB1 alleles and/or TNF microsatellite polymorphisms. Methods. The frequencies of HLA-DRB1 alleles and TNF microsatellite polymorphisms were compared between RA patients with and without extraarticular disease in a population from Lugo, NW Spain. HLA-DRB1 and TNF typing were carried out using molecular based methods on 181 clinic-based RA patients and 145 healthy controls. Associations were investigated using Chi-square analyses or Fisher's exact test. Multivariate logistic regression analyses were used to investigate independent and interactive effects of HLA and TNF alleles. Results. The frequencies of HLA-DRB1 and TNF microsatellite polymorphisms in patients with EAM were not significantly different from those without extraarticular disease, although an association between HLA-DRB1*0101 and nodular disease approached significance (p = 0.054). There was no evidence for an increased frequency of homozygous or heterozygous combinations of disease associated DRB1 alleles in RA patients with EAM. The TNF a8 microsatellite allele was found at a higher frequency (6.9%) in patients with EAM compared to those without EAM (1.8%), and controls (1.5%) (p = 0.03 and 0.02, respectively). However, significance was lost after correction for multiple testing. No evidence was found for an interaction between HLA-DRB1 and TNF alleles being associated with the expression of EAM. Conclusion. In an RA population from NW Spain the frequencies of HLA-DRB1 and TNF microsatellite alleles in patients with extra-articular manifestations were not significantly different to those without extraarticular disease, although there was a trend towards increased frequency of HLA-DRB1*0101 in patients with nodular disease. There was no evidence for an interaction between HLA-DRB1 and TNF alleles in relation to the expression of EAM.