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

Hui Ying Xu,Zhang Yang Wang,Bi-Cheng Chen,Xian-Yang Lin,Jing Feng Chen,Li Li Tang,Ling Ling Wang,Chun-Wu Zhang,Tian Yang Wang

doi:10.1371/journal.pone.0122055

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.

Highlights

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain
102 AS patients and 105 healthy individuals were successfully genotyped for their rs2910164 G/C and rs3746444 T/C Single-nucleotide polymorphisms (SNPs)
The miR-499 rs3746444 T/C SNP showed no association with the susceptibility of AS at the allele level (75.0% vs. 85.2%, P = 0.369, power = 15%)

Summary

Introduction

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain. It can lead to structural and functional impairments and a decrease in quality of life. MiR-146a/miR-499 Polymorphisms and Ankylosing Spondylitis ambiguous, it is likely that AS is a multifactorial disease, influenced by genetic and environmental factors. It is conceivable that the HLA-B27 gene is the most important risk factor for AS. Many genes in and outside the MHC, as yet largely undefined, have been demonstrated to be associated with the development of AS

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Results

Conclusion