Background The Fc receptor-like 3 gene (FCRL3) is located on chromosome 1q21, a region implicated in susceptibility to several autoimmune diseases by whole-genome linkage studies. The FCRL3 protein is an orphan cell surface receptor with homology to Fc immunoreceptors and is expressed predominantly in B lymphocytes in lymph nodes and germinal centers. Moreover, the functional -169 C/T promoter polymorphism of FCRL3 was shown to confer susceptibility to autoimmune diseases in a Japanese population. The FCRL3 -169 C allele was found to produce higher promoter activity in a reporter gene assay and to be more avidly bound by NF-kB in gel-shift studies, which suggests that it has a direct functional role.
Objectives The aim of this study was to determine whether the functional Fc receptor like-3 (FCRL3) -169 C/T polymorphism confers susceptibility to rheumatoid arthritis (RA).
Methods MEDLINE and EMBASE database and manual search were utilized to identify to identify articles in which the FCRL3 -169 C/T polymorphism was determined in RA patients and controls. A meta-analysis was conducted on the associations between the FCRL3 -169 C/T polymorphism and RA using; 1) allelic contrast, 2) recessive models, 3) dominant models, and 4) homozygote contrast.
Results A total of 17 comparison studies including 11,170 patients and 11,142 controls were considered in the meta-analysis. The meta-analysis showed no association between RA and the FCRL3 -169 C allele in study subjects (OR = 1.046, 95% CI = 0.997–1.098, p = 0.068). Stratification by ethnicity indicated an association between the FCRL3 -169 C allele and RA in Asians (OR = 1.101, 95% CI = 1.035–1.174, p = 0.002), but not in Europeans. Stratification of patients according to the presence of rheumatoid factor (RF) revealed a different significant association between the C allele and RA in RF-positive and RF-negative RA patients. Stratification by ethnicity indicated an association between the FCRL3 -169 C allele and RF-positive RA in Asians (OR = 1.093, 95% CI = 1.004–1.189, p = 0.040), but not in Europeans.
Conclusions This meta-analysis demonstrates that the FCRL3 -169 C/T polymorphism may confer susceptibility to seropositive RA in Asians.
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Disclosure of Interest None Declared