FCRL3 promoter 169 CC homozygosity is associated with susceptibility to rheumatoid arthritis in Dutch Caucasians

• Published in: Annals of the rheumatic diseases 2007-06, Vol.66 (6), p.803-806
• Main Authors: Thabet, Mohamed M, Wesoly, J, Slagboom, P E, Toes, R E M, Huizinga, T W J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anti-CCP; anticyclic citrullinated peptide antibody; Arthritis, Rheumatoid - genetics; Binding sites; Biological and medical sciences; Diseases of the osteoarticular system; Extended Report; Female; Freeware; Gene Frequency; Genes; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Heterozygote; HLA; Homozygote; human leucocyte antigen; Humans; Inflammatory joint diseases; linkage disequilibrium; Male; Medical sciences; Middle Aged; Pathogenesis; Polymorphism, Single Nucleotide; Population; Promoter Regions, Genetic; Receptors, Immunologic - genetics; rheumatoid arthritis; Severity of Illness Index; shared epitope; single-nucleotide polymorphism; SNP; Software packages; Studies; White people
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2006.064949

Background: Human leucocyte antigen is the only genetic risk factor for rheumatoid arthritis (RA) that has been 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 Dutch Caucasian patients with RA, as well as to perform 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 four FCRL3 single-nucleotide polymorphisms (SNPs). Genotyping was performed using the MassArray matrix-assisted laser desorption ionisation-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 the association of CC genotype with a higher risk of developing RA as compared with TT and TC carriers (p = 0.039 and OR = 1.31). There was no significant difference in the genotype and allele frequencies of all investigated SNPs between cases and controls. Meta-analysis of all studies comparing 9467 individuals showed that the OR for the CC genotype to develop RA was 1.2 and the p value