Association between ankylosing spondylitis and the miR-146a and miR-499 polymorphisms

Abstract

miRNAs are small, non-coding RNAs that regulate the expression of multiple target genes at the post-transcriptional level. Single-nucleotide polymorphisms (SNPs) in miRNA sequences may alter miRNA expression and have been implicated in the pathogenesis of multiple forms of arthritis, including rheumatoid arthritis (RA) and osteoarthritis. The present study explored the association between ankylosing spondylitis (AS) and two single nucleotide polymorphisms (SNPs), miR-146a rs2910164G>C and miR-499 rs3746444T>C, in a Han Chinese population. A case-control study consisting of 102 subjects with AS and 105 healthy controls was designed. The two miRNA SNPs were identified by direct sequencing. Subsequently, their gene and genotype frequencies were compared with healthy controls. A significant difference was observed in the miR-146a rs2910164G>C SNP. The frequency of the G allele was markedly higher in the AS patients than in the healthy controls (P = 0.005, Pc = 0.01, OR = 1.787), and the frequency of the GG genotype was higher in AS patients than in controls (P = 0.014, Pc = 0.042, OR = 2.516). However, no significant association was found between the miR-499 rs3746444T>C variant and susceptibility to AS. This is the first study to address the association between the miR-146a rs2910164G>C and miR-499 rs3746444T>C polymorphisms and AS, and it suggests a potential pathogenic factor for AS. Further studies are needed to validate our findings in a larger series, as well as in other ethnic backgrounds.

Fig 1. Association between variants of miR-146a (rs2910164) and miR-499 (rs3746444) and activity parameters.

A. The levels of CRP among different miR-146a genotypes. No significant differences were found (CC vs. GG, P = 0.43; CC vs. GC, P = 0.79; GG vs. GC, P = 0.515). B. The levels of ESR among miR-146a genotypes. There were no significant differences among the three genotypes (CC vs. GG, P = 0.222; CC vs. GC, P = 0.249; GG vs. GC, P = 0.782). C. The levels of CRP among different miR-499 genotypes. No significant differences were found (TT vs. TC, P = 0.607). D. The levels of ESR among miR-499 genotypes. There were no significant differences (TT vs. TC, P = 0.759).