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强直性脊柱炎与miR-146a及miR-499基因多态性之间的关联。

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

作者信息

Xu Hui Ying, Wang Zhang Yang, Chen Jing Feng, Wang Tian Yang, Wang Ling Ling, Tang Li Li, Lin Xian-yang, Zhang Chun-wu, Chen Bi-cheng

机构信息

Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.

Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.

出版信息

PLoS One. 2015 Apr 2;10(4):e0122055. doi: 10.1371/journal.pone.0122055. eCollection 2015.

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.

摘要

微小RNA(miRNA)是一类小的非编码RNA,它们在转录后水平调节多个靶基因的表达。miRNA序列中的单核苷酸多态性(SNP)可能会改变miRNA的表达,并与多种形式的关节炎(包括类风湿性关节炎(RA)和骨关节炎)的发病机制有关。本研究探讨了汉族人群中强直性脊柱炎(AS)与两个单核苷酸多态性(SNP),即miR-146a rs2910164G>C和miR-499 rs3746444T>C之间的关联。设计了一项病例对照研究,包括102例AS患者和105名健康对照。通过直接测序鉴定了这两个miRNA SNP。随后,将它们的基因和基因型频率与健康对照进行比较。在miR-146a rs2910164G>C SNP中观察到显著差异。AS患者中G等位基因的频率明显高于健康对照(P = 0.005,Pc = 0.01,OR = 1.787),并且AS患者中GG基因型的频率高于对照(P = 0.014,Pc = 0.042,OR = 2.516)。然而,未发现miR-499 rs3746444T>C变体与AS易感性之间存在显著关联。这是第一项探讨miR-146a rs2910164G>C和miR-499 rs3746444T>C多态性与AS之间关联的研究,它提示了AS的一个潜在致病因素。需要进一步的研究在更大的样本系列以及其他种族背景中验证我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7094/4383612/bddcd52e600f/pone.0122055.g001.jpg

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