Epistatic interaction between FCRL3 and NFκB1 genes in Spanish patients with rheumatoid arthritis

Background: A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the F-c receptor-like 3 (FCRL3) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21-23. Objectives: To evaluate the association between rheumatoid arthritis and FCLR3 polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the FCRL3 polymorphisms and the transcription factor nuclear factor kappa B (NF kappa B), a functional polymorphism located in the NF kappa B1 gene was included. Methods: 734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the FCRL3 gene were studied by TaqMan technology. The -94ins/delATTG NF kappa B1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 362 contingency tables and chi(2) values. Results: No overall differences were found in any of the FCRL3 polymorphisms and in the NFkB1 promoter polymorphism when patients were compared with controls. However, when stratified according to NF kappa B1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NF kappa B1 (p(c) = 0.003). Conclusions: The FCRL3 polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between NFkB1 and FCRL3 in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations.