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  • Title: A genetic association study of the CLEC12A gene in rheumatoid arthritis.
    Author: Michou L, Cornélis F, Levesque JM, Bombardieri S, Balsa A, Westhovens R, Barrera P, Alves H, van de Putte L, Migliorini P, Bardin T, Petit-Teixeira E, Fernandes MJ.
    Journal: Joint Bone Spine; 2012 Oct; 79(5):451-6. PubMed ID: 22341585.
    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). CONCLUSION: 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.
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