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miRNA-146a 基因的遗传变异:系统性红斑狼疮易感性、狼疮性肾炎和疾病活动的指标。

Genetic variants of microRNA-146a gene: an indicator of systemic lupus erythematosus susceptibility, lupus nephritis, and disease activity.

机构信息

Clinical Pathology Department, Benha Faculty of Medicine, Benha University, Benha, Egypt.

Rheumatology, Rehabilitation and Physical Medicine Department, Benha Faculty of Medicine, Benha University, Benha, Egypt.

出版信息

Mol Biol Rep. 2020 Oct;47(10):7459-7466. doi: 10.1007/s11033-020-05802-y. Epub 2020 Sep 14.

Abstract

Genetic variations of microRNA encoding genes influence various sorts of diseases by modifying the expression or activity of microRNAs. MicroRNA 146a is an epigenetic regulator of immune response through controlling the type I interferon (IFN) and nuclear factor kappa B (NF-κB) pathways. Genetic variations of microRNA 146a impact the susceptibility to systemic lupus erythematosus (SLE) and its clinical presentations. This study aimed to investigate the polymorphisms of microRNA-146a gene (rs2431697 and rs57095329) in patients with SLE and its association with disease activity. Sixty-five patients with SLE and 40 apparently healthy controls were enrolled in this study. Patients were subjected to history taking, clinical examination, and disease activity evaluation by SLEDAI score. The microRNA-146a variants were determined by allele discrimination real-time PCR method in all participants. We found a statistically significant association between rs2431697 T allele and SLE (P-value < 0.05), but there was no significant association between rs57095329 and SLE. The T/T genotype of microRNA-146a rs2431697 was associated with lupus nephritis, higher disease activity, and autoantibodies production. The microRNA-146a rs2431697 T allele could be a potential risk factor that contributes to SLE susceptibility, development of lupus nephritis, and disease activity.

摘要

miRNA 编码基因的遗传变异通过改变 miRNA 的表达或活性来影响各种疾病。miRNA-146a 是通过控制 I 型干扰素 (IFN) 和核因子 kappa B (NF-κB) 途径对免疫反应的表观遗传调节剂。miRNA-146a 的遗传变异影响系统性红斑狼疮 (SLE) 的易感性及其临床表现。本研究旨在探讨 miRNA-146a 基因 (rs2431697 和 rs57095329) 多态性与 SLE 患者疾病活动的关系。本研究纳入 65 例 SLE 患者和 40 名健康对照者。对患者进行病史采集、临床检查和 SLEDAI 评分评估疾病活动度。采用等位基因鉴别实时 PCR 法检测所有参与者的 miRNA-146a 变异。我们发现 rs2431697 T 等位基因与 SLE 之间存在统计学显著关联(P 值 < 0.05),但 rs57095329 与 SLE 之间无显著关联。miRNA-146a rs2431697 的 T/T 基因型与狼疮肾炎、更高的疾病活动度和自身抗体产生有关。miRNA-146a rs2431697 的 T 等位基因可能是 SLE 易感性、狼疮肾炎发展和疾病活动的潜在危险因素。

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