title: Association of the FCRL3 gene with rheumatoid arthritis: a further example of population specificity?
abstract: Association of a functional promoter polymorphism mapping to the Fc receptor-like 3 (FCRL3) gene has recently been reported and replicated with rheumatoid arthritis (RA) in Japanese populations. The aim of this study was to investigate association of the FCRL3 gene with RA in UK subjects. DNA was available from 1065 patients with RA and 2073 population controls from the UK. Four single nucleotide polymorphism (SNP) markers (FCRL3-169*C/T (fclr3_3, rs7528684), fclr3_4 (rs11264799), fclr3_5 (rs945635), fclr3_6 (rs3761959)) all previously associated with RA in a Japanese population were genotyped in 761 RA samples and 484 controls. In the remaining samples, only the putative disease causal polymorphism, FCRL3-169*C/T, was tested. Genotyping was performed using either the Sequenom MassArray iPlex platform or a 5' Allelic discrimination assay (Taqman, ABI). Extensive linkage disequilibrium was present across the promoter SNPs genotyped (r2 values = 0.60-0.98). Allele frequencies did not differ between RA cases and controls either for the putative disease causal polymorphism (odds ratio FCRL3-169*C allele = 0.97 (0.87-1.07), p = 0.51) or for the other SNPs tested. Similarly, no association was detected with RA using haplotype analysis or when stratification by shared epitope carriage or by presence of rheumatoid factor was undertaken. This study was powered to detect an effect size of 1.24 or greater for the FCRL3-169*C/T functional promoter polymorphism but no evidence for association was detected, suggesting that this gene will not have a substantial effect in determining susceptibility to RA in populations of Northern European descent.
authors.affiliation: ARC-EU, University of Manchester, UK. stephen.eyre@manchester.ac.uk
authors.forename: Stephen
authors.initials: S
authors.lastname: Eyre
authors.forename: John
authors.initials: J
authors.lastname: Bowes
authors.forename: Catherine
authors.initials: C
authors.lastname: Potter
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D003596:Cytosine; D000939:Epitopes / Q000235:genetics; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D012217:Rheumatoid Factor / Q000097:blood; D013941:Thymine; D006113:United Kingdom
chemical_list: D000939:Epitopes; C457775:FCRL3 protein, human; D005819:Genetic Markers; D011971:Receptors, Immunologic; D003596:Cytosine; D012217:Rheumatoid Factor; D013941:Thymine