A polymorphism in the 3′-UTR of interleukin-1 receptor-associated kinase (IRAK1), a target gene of miR-146a, is associated with rheumatoid arthritis susceptibility

Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disorder with many genetic factors predisposing to disease susceptibility. MicroRNAs are a new discovered class of molecules that participate in post-transcriptional regulation of genes' expression. MicroRNA-146a was found to be increased in synovial fibroblasts, synovial tissue and PBMC from patients with RA. The aim of the present study was to reveal if there is any association of miRNA-146a variant rs2910164 and the two interleukin (IL) 1 receptor associated kinase (IRAK1, a target gene of mir-146a) polymorphisms rs3027898 and rs1059703 with RA predisposition. Methods: One hundred and thirty-six RA patients and 147 controls were enrolled in the study. Results: Strong statistically significant difference was observed in IRAK1 rs3027898 A>C polymorphism distribution between RA patients and controls (p = 0.044), which was higher comparing the distribution of allele A vs. allele C between the studied groups (p = 0.017). Conclusion: This is the first study that addresses association of a variant in a target of miR-146a, IRAK1 gene, with RA susceptibility. Further studies in other ethnic groups of patients could help to understand the extent of the proposed association. (C) 2010 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.