Background:HLA is the only genetic risk factor for rheumatoid arthritis (RA) that was consistently observed in different populations. A number of other genes such as PTPN22 and PADI4 showed population specific association with RA susceptibility. Recently Fc receptor-like 3 (FCRL3) gene was found to be associated with RA susceptibility in Japanese, but with conflicting results in other populations.
Objective: To investigate the association of FCRL3 polymorphism with RA susceptibility and severity in the Dutch Caucasian RA patients, as well as performing a meta-analysis to reveal the contribution of this gene to RA susceptibility.
Methods: A total of 931 Dutch RA cases and 570 unrelated Dutch controls were genotyped for 4 FCRL3 single nucleotide polymorphisms (SNPs). Genotyping was performed using the MassArray matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Association of the FCRL3 SNPs with Susceptibility to RA was examined by single-marker, carrier and haplotype analysis.
Results: Carrier analysis of the SNP (rs7528684) revealed association of CC genotype with higher risk of developing RA as compared to TT&TC carriers (P=0.039 and OR=1.31). There was no significant difference in the genotype and allele frequency of all investigated SNPs between cases and controls. Meta-analysis of all studies comparing 9467 individuals showed that the odds ratio for the CC genotype to develop RA was 1.2 and the P- value < 0.001.
Conclusion:. A promoter polymorphism of FCRL3 (rs7528684) is associated with an increased risk to develop RA in Dutch Caucasians, suggesting that this association is relevant for RA in both Japanese and Caucasian populations.