FCRL3 gene polymorphisms as risk factors for rheumatoid arthritis

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. As a member of FCRLs clusters, Fc receptor-like 3 (FCRL3) has been recognized as a neoteric autoimmune activation factor for RA. The aim of our study is to evaluate the correlation between four single-nucleotide polymorphisms (SNPs) on FCRL3 and RA risk in a Chinese Han population.

The hospital-based case-control study included 630 RA patients together with 696 healthy individuals as the control group and all subjects are Chinese ancestry. Four tagging single-nucleotide polymorphisms (tag-SNPs) on FCRL3 were selected and genotyped by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to evaluate the correlations between FCRL3 polymorphisms and RA. A systematic meta-analysis was also carried out based on the present study and previously published studies to further examine the association between FCRL3 variations and RA risk.

Significant association was found between -169T/C SNP and RA risk (CC vs. TT, OR=1.62, 95% CI=1.18-2.22; TC/CC vs. TT, OR=1.47, 95% CI=1.18-1.84; C vs. T, OR=1.32, 95% CI=1.12-1.54). Apart from that, mutations of -169T/C was significantly correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positive status. The meta-analysis also suggested that -169T/C mutation might have positive correlation with risk of RA in the overall population, particularly for Asian. Stratified analysis based on clinical characteristics of RF and ACPA also provided evidence that -169T/C polymorphisms could alter phenotypes of RA.

The FCRL3 -169T/C variant was significantly linked with an increased RA risk in the Chinese Han population. Moreover, this meta-analysis also provides notion that -169T/C variant could act as a susceptible factor for RA. However, further investigations about the functional impacts of this polymorphism are essential to confirm the above conclusions.