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白细胞介素-1 受体相关激酶 1(IRAK1)的 3'-UTR 中的多态性是 miR-146a 的靶基因,与类风湿关节炎易感性相关。

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.

机构信息

Genetics Unit, Department of Obstetrics and Gynaecology, University of Ioannina, Ioannina, Greece.

出版信息

Joint Bone Spine. 2010 Oct;77(5):411-3. doi: 10.1016/j.jbspin.2010.05.013. Epub 2010 Sep 25.

Abstract

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.

摘要

目的

类风湿关节炎(RA)是一种慢性炎症性疾病,有许多遗传因素导致疾病易感性。 microRNA 是一类新发现的分子,参与基因表达的转录后调控。在 RA 患者的滑膜成纤维细胞、滑膜组织和 PBMC 中发现 microRNA-146a 增加。本研究的目的是揭示 microRNA-146a 变异 rs2910164 与两个白细胞介素(IL)1 受体相关激酶(IRAK1,mir-146a 的靶基因)多态性 rs3027898 和 rs1059703 与 RA 易感性之间是否存在关联。

方法

本研究纳入了 136 名 RA 患者和 147 名对照者。

结果

在 RA 患者和对照组之间,IRAK1 rs3027898 A > C 多态性分布存在显著统计学差异(p = 0.044),在研究组之间,与等位基因 C 相比,等位基因 A 的分布更高(p = 0.017)。

结论

这是第一项研究表明,miR-146a 的靶基因 IRAK1 基因中的变异与 RA 易感性有关。在其他患者群体中的进一步研究可以帮助了解所提出的关联的程度。

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