The −169C/T polymorphism in FCRL3 is not associated with susceptibility to rheumatoid arthritis or systemic lupus erythematosus in a case–control study of Koreans

Abstract

Objective. In Japanese individuals, the ؊169C/T single-nucleotide polymorphism (SNP) in FCRL3 has been reported to be associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and autoimmune thyroid diseases. The objective of this study was to test the association of this SNP with RA and SLE, in a case-control study of Korean individuals.Methods. The ؊169C/T SNP in FCRL3 was genotyped in 1,060 patients with RA, 457 patients with SLE, and 697 unaffected control subjects, using the Mass-ARRAY SNP genotyping system. Associations were tested by multivariate logistic regression, with adjustments for age and sex.Results. No association was detected between the ؊169C/T SNP and RA (odds ratio [OR] 1.11, 95% confidence interval [95% CI] 0.83-1.48, P ‫؍‬ 0.50) or SLE (OR 1.00, 95% CI 0.73-1.37, P ‫؍‬ 0.99). This SNP was not associated with rheumatoid factor status, shared epitope status, radiographic severity in patients with RA, or disease manifestations in patients with SLE.Conclusion. The association of the ؊169C/T SNP in FCRL3 with RA and SLE that was observed in Japanese patients was not replicated in a Korean population.

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

“…Its function is not known well, but it might have a regulatory function in signal transduction. 89 The À169C/ T variant of the FCRL3 gene showed an association with SLE in Japanese 89 but not in Korean 90 and Spanish 91 populations. Instead, the FCRL haplotype (Fcr3/4/6) showed a weak association with SLE (OR ¼ 1.32; P ¼ 0.04) in a Spanish population.…”

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

“…However, they failed to confirm the positive correlation between serum RF levels and FCRL3 genotype (information on anti-CCP and SE status was not reported). Of interest, in a recent large Korean case-control study with 1,060 patients and 697 controls, the FCRL3 polymorphism was not significantly associated with RA (allelic OR 1.10, P exact ϭ 0.163; recessive model OR 1.04, P exact ϭ 0.801), even after stratification by RF and SE status (9).…”

“…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). Although the precise function of FCRL3, which has strong structural homology with the classic Fc␥ receptors, is unknown, the existing data are consistent with the hypothesis that it may influence the fate of B cells and augment the emergence of self-reactive cells in the germinal center (for review, see ref.…”

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

“…This SNP was found to occur within a consensus binding site for the transcription factor NF-jB, resulting in a functional alteration of the NF-jB binding as well as altered FCRL3 gene transcription. 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).…”