Epistatic interaction between FCRL3 and NF B1 genes in Spanish patients with rheumatoid arthritis

Abstract

Background: A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc 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 kB (NFkB), a functional polymorphism located in the NFkB1 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 294ins/delATTG NFkB1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 362 contingency tables and x 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 NFkB1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NFkB1 (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.

Interleukin‐10 Gene Promoter and NFKB1 Promoter Insertion/Deletion Polymorphisms in Systemic Sclerosis

“…A meta-analysis suggests an association between NFKB1 to certain autoimmune and inflammatory diseases in the Asian population, but not in the Caucasian population [33]. Likewise, our study found no association of NFKB1 polymorphism with SSc.…”

Meta‐analysis evidence of a differential risk of the FCRL3 −169T→C polymorphism in white and East Asian rheumatoid arthritis patients

“…Studies of 2 independent North American RA sample sets (3), a large UK sample set (4), and a sample set from New Zealand (5) showed no evidence of association of the SNP with RA (Table 1). A similar finding was obtained in a study of whites of Spanish origin, although, when the authors combined their 2 sample sets and stratified patients and controls by genotype at a putative NFKB1 promoter polymorphism, Ϫ94ins/delATTG, the distribution of FCRL3 Ϫ169T3 C genotypes was significantly different between patients and controls who were heterozygous for the NFKB1 polymorphism (P ϭ 0.001) (6).…”

“…Studies examining the role of this polymorphism in risk of RA in 9 independent white sample sets, however, have yielded conflicting results (3)(4)(5)(6)(7)(8). Further, a large study of Korean subjects failed to demonstrate association of this single-nucleotide polymorphism (SNP) with RA (9).…”

Replication of reported genetic associations of PADI4, FCRL3, SLC22A4 and RUNX1 genes with rheumatoid arthritis: results of an independent Japanese population and evidence from meta-analysis of East Asian studies

“…The association between fcrl3_3 and RA was replicated in an independent Japanese case-control sample collection in a separate study (Ikari et al 2006b), while a large study of Korean subjects failed to demonstrate a significant effect (Choi et al 2006). Several studies have assessed the role of fcrl3_3 in the development of RA in Caucasians, and many failed to replicate the earlier results (Martinez et al 2006a;Eyre et al 2006;Newman et al 2006;Thabet et al 2007). A recent meta-analysis involving more than 10,000 white subjects provided no evidence of association (Begovich et al 2007).…”