Association of microRNA-146a and its target gene IRAK1 polymorphism with enthesitis related arthritis category of juvenile idiopathic arthritis

Abstract

MicroRNAs (miRNAs) are non-coding RNA that modulate the expression of multiple target genes at the post-transcriptional level. Single-nucleotide polymorphisms (SNPs) in pre-miRNAs can alter miRNA expression, and polymorphism in target molecules can affect binding to target mRNA. Studies have shown an association between miR-146a gene polymorphism and autoimmune diseases. A target for miR-146a is IRAK1. We studied the SNPs of miRNA-146 and IRAK1 to see their association with susceptibility to juvenile idiopathic arthritis-enthesitis-related arthritis (JIA-ERA). One hundred and fifty patients with JIA-ERA (ILAR criteria) were included in the study. A total of 216 blood donors (201 male) with a mean age of 30.5 years served as controls. miR-146a (rs2910164) and its target IRAK1 (rs1059703) at exon-12 region and IRAK1 (rs3027898) at 3'UTR polymorphisms were analyzed using PCR-RFLP method. Among 150 patients, 133 were males and the mean age at onset of disease was 11 (4-16) years, mean disease duration was 4.5 (0.3-12) years. Twenty-two had uveitis and 21 had positive family history of spondyloarthropathy, 73 had enthesitis, 75 had inflammatory back pain, and all had arthritis. HLA B27 was present in 116 patients. Genotype frequency of miR-146a gene was in Hardy-Weinberg equilibrium in healthy controls. The genotype frequency for miR-146a was different in controls and patients [GG (51.85 vs. 50.0 %), GC (42.13 vs. 37.29 %) and CC (6.02 vs. 12.71 %), OR = 2.18; 95 % CI 1.02-4.68; p value = 0.0418]. The allele frequencies of IRAK1 (rs1059703) and IRAK1 (rs3027898) in males and genotype frequency in females were similar in controls and patients. The C allele of IRAK1 (rs1059703) was in linkage disequilibrium with T allele of IRAK1 (rs3027898). The CC genotype of the miR-146a rs2910164 polymorphism was significantly associated with the susceptibility to JIA-ERA.