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 40IU/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.

A genetic association study of the CLEC12A gene in rheumatoid arthritis

BOMBARDIERI, STEFANO;MIGLIORINI, PAOLA;
2012

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 40IU/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.
Michou, L; Cornelis, F; Levesque, Jm; Bombardieri, Stefano; Balsa, A; Westhovens, R; Barrera, P; Alves, H; VAN DE PUTTE, L; Migliorini, Paola; Bardin, T; PETIT TEIXEIRA, E; Fernandes, M. J.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/193000
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