title: A genetic association study of the CLEC12A gene in rheumatoid arthritis.
abstract: OBJECTIVE
  The CLEC12A gene codes for an immune inhibitory receptor that maps to 12p13.2. Since an increase in CLEC12A mRNA correlates with rheumatoid factor values greater than 40 IU/ml in rheumatoid fibroblast-like synovial cells, this study assessed the potential of an association between CLEC12A and rheumatoid arthritis (RA) using a phenotype-based approach.
  
  
  METHODS
  A discovery cohort of Western European ethnicity was genotyped for eight tag single nucleotide polymorphisms. Statistical analyses relied on the transmission disequilibrium test, relative risk and 95% confidence interval (CI) calculations. Observed haplotype frequencies were compared to expected frequencies using a family-based association test. Statistically significant associations were further tested in a second cohort of unrelated West-European RA patients.
  
  
  RESULTS
  An overtransmission of the C allele of the rs1323461 tag single nucleotide polymorphism was observed (56.6% of allele C transmission, P = 0.046) in the discovery cohort. The relative risk of the AC and CC genotypes when compared to the AA genotype was high (relative risk = 4.08; 95% CI: 1.52-10.95, uncorrected P = 2.1 × 10(-3)), particularly in the subgroup of erosive RA (relative risk = 5.27; 95% CI: 1.53-18.19, uncorrected P = 2.1 × 10(-3)), both remaining statistically significant after conservative Bonferroni's correction. The CGAGCCGA haplotype was observed more frequently than expected (P = 0.013). In the second cohort, the C allele had a tendency to be more frequent in RA patients (82.4%) than controls (79.2%) (P = 0.069).
  
  
  CONCLUSIONS
  We report a potential genetic association of CLEC12A with RA. Since CLEC12A encodes for the myeloid inhibitory C-type lectin-like receptor that modulates cytokine synthesis, this receptor may contribute to the pathogenesis of RA.
authors.affiliation: Department of Medicine, Laval University, CHUQ, CHUL, Research Centre and Division of Rheumatology, CHUQ, CHUL, Quebec City, QC, Canada.
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Michou
authors.forename: François
authors.initials: F
authors.lastname: Cornélis
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Levesque
authors.forename: Stefano
authors.initials: S
authors.lastname: Bombardieri
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: René
authors.initials: R
authors.lastname: Westhovens
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Helena
authors.initials: H
authors.lastname: Alves
authors.forename: Leo
authors.initials: L
authors.lastname: van de Putte
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petit-Teixeira
authors.forename: Maria J G
authors.initials: MJ
authors.lastname: Fernandes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011975:Receptors, Mitogen / Q000235:genetics*
chemical_list: C485220:CLEC12A protein, human; D037181:Lectins, C-Type; D011975:Receptors, Mitogen