A genetic association study of the CLEC12A gene in rheumatoid arthritis

作者：Michou Laetitia; Cornelis Francois; Levesque Jean Michel; Bombardieri Stefano; Balsa Alejandro; Westhovens Rene; Barrera Pilar; Alves Helena; van de Putte Leo; Migliorini Paola; Bardin Thomas; Petit Teixeira Elisabeth; Fernandes Maria J G^*

来源：Joint Bone Spine, 2012, 79(5): 451-456.

DOI：10.1016/j.jbspin.2011.12.012

• Rheumatoid arthritis
• CLEC12A gene
• Candidate gene study
• Single nucleotide polymorphism
• Haplotype

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. %26lt;br%26gt;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. %26lt;br%26gt;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 x 10-3), particularly in the subgroup of erosive RA (relative risk = 5.27; 95% CI: 1.53-18.19, uncorrected P = 2.1 x 10(-3)), both remaining statistically significant after conservative Bonferroni%26apos;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). %26lt;br%26gt;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.

• 出版日期2012-10