title: Development of rheumatoid arthritis is not associated with two polymorphisms in the Crohn's disease gene CARD15.
abstract: BACKGROUND
  It has been proposed that genetic susceptibility loci for rheumatoid arthritis (RA) may be shared with other autoimmune/inflammatory diseases. Recently, common variation in the CARD15 (NOD2) gene on chromosome 16q12 has been associated with Crohn's disease (CD) in several independent populations. CARD15 is an excellent functional and positional candidate gene for RA.
  
  
  METHODS
  Genomic DNA was obtained from 392 RA cases and 471 ethnically matched healthy controls. All samples were genotyped for two polymorphisms in CARD15, 1007fs and R702W, using 5' nuclease reporter assays. Allele frequencies were compared between cases and controls using the chi(2) test. Estimated haplotype frequencies across the two mutations were determined using the EH program.
  
  
  RESULTS
  The allele frequency of the 1007fs variant in RA cases was 1.8% compared with 1.6% in normal controls (not significant). The frequency of the R702W variant was 4.0% in both cases and controls. Haplotypes carrying either of the two mutations accounted for 5.6% of possible haplotypes. A haplotype carrying both mutations was rare, with estimated frequency <0.01%. This study provided high power to detect an association of similar magnitude to that in Crohn's disease. These data therefore exclude the possibility that the contribution of these mutations to RA is comparable to that seen in CD.
  
  
  CONCLUSIONS
  Within defined statistical parameters, we excluded a role for the CARD15 1007fs and R702W variants in RA susceptibility. These data do not preclude a role for other polymorphisms in the CARD15 gene in RA susceptibility. Results from other autoimmune and inflammatory diseases will reveal whether the CARD15 gene is in fact a common autoimmune susceptibility locus.
authors.affiliation: Molecular Immunogenetics, Department of Rheumatology, Division of Medicine, Guy's, King's and St Thomas' School of Medicine, Guy's Hospital Campus, King's College, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Steer
authors.forename: S A
authors.initials: SA
authors.lastname: Fisher
authors.forename: M
authors.initials: M
authors.lastname: Fife
authors.forename: A
authors.initials: A
authors.lastname: Cuthbert
authors.forename: J
authors.initials: J
authors.lastname: Newton
authors.forename: P
authors.initials: P
authors.lastname: Wordsworth
authors.forename: C M
authors.initials: CM
authors.lastname: Lewis
authors.forename: C G
authors.initials: CG
authors.lastname: Mathew
authors.forename: J S
authors.initials: JS
authors.lastname: Lanchbury
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16; D003424:Crohn Disease / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein