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.
Kochi Y, Yamada R, Suzuki A, Harley JB, Shirasawa S, Sawada T, Bae SC, Tokuhiro S, Chang X, Sekine A, Takahashi A, Tsunoda T, Ohnishi Y, Kaufman KM, Kang CP, Kang C, Otsubo S, Yumura W, Mimori A, Koike T, Nakamura Y, Sasazuki T and Yamamoto K (2005) A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nat Genet 37:478-85.
Kyogoku C, Dijstelbloem HM, Tsuchiya N, Hatta Y, Kato H, Yamaguchi A, Fukazawa T, Jansen MD, Hashimoto H, van de Winkel JG, Kallenberg CG and Tokunaga K (2002) Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Arthritis Rheum 46:1242-54.
Davis RS, Dennis G, Jr., Odom MR, Gibson AW, Kimberly RP, Burrows PD and Cooper MD (2002) Fc receptor homologs: newest members of a remarkably diverse Fc receptor gene family. Immunol Rev 190:123-36.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.