Department of Clinical and Chemical Pathology, Sohag University, Sohag, Egypt.
Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Immun Inflamm Dis. 2020 Dec;8(4):595-604. doi: 10.1002/iid3.344. Epub 2020 Aug 27.
MicroRNAs are large family clusters of small noncoding RNAs that implicated in genetic and epigenetic regulation of several immunological processes and pathways. As an epigenetic modifier, the microRNA 17-92 cluster host gene (MIR17HG) has been shown to regulate the expression of genes involved in systemic lupus erythematosus (SLE) pathway. This study aimed to explore the association of MIR17HG (rs4284505; A>G) variant with SLE development and phenotype in a sample of the Eastern Mediterranean population.
A total of 326 participants (163 patients with SLE and 163 healthy controls) were enrolled in this study. The different genotypes of the MIR17HG (rs4284505) variant were characterized using the TaqMan real-time polymerase chain reaction technique. Association with the available clinical and laboratory data, including the systemic lupus erythematosus disease activity index (SLEDAI), was also executed.
The MIR17HG (rs4284505) variant showed a protective effect against developing SLE under heterozygote (A/G vs A/A; odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.05-0.20, P < 0.001) and dominant (A/G+G/G vs A/A; OR = 0.39, 95% CI = 0.25-0.61, P < .001) models. This association was consistent even after SLE stratified by lupus nephritis. In contrast, rs4284505 (G/G) genotype conferred increased susceptibility to SLE (G/G vs A/A+A/G; OR = 2.15, 95% CI = 1.31-3.53, P = .002). Moreover, the rs4284505 variant showed a statistically significant association with mucocutaneous lesions and SLEDAI scores (all P < .05).
This study is the first one to explore that the MIR17HG rs4284505 is associated with SLE risk; (A/G) genotype conferred a protective effect, while the (G/G) genotype showed increased susceptibility to SLE and association with the disease severity in the study population.
微小 RNA 是一组大型的非编码 RNA 小家族，参与了几个免疫过程和途径的遗传和表观遗传调控。作为一种表观遗传修饰物，miRNA17-92 簇宿主基因（MIR17HG）已被证明可以调节系统性红斑狼疮（SLE）途径中涉及的基因表达。本研究旨在探讨 MIR17HG（rs4284505；A>G）变体与东地中海人群中 SLE 发病和表型的关联。
共纳入 326 名参与者（163 名 SLE 患者和 163 名健康对照者）。采用 TaqMan 实时聚合酶链反应技术对 MIR17HG（rs4284505）变体的不同基因型进行特征分析。还对与 SLE 相关的临床和实验室数据进行了关联分析，包括系统性红斑狼疮疾病活动指数（SLEDAI）。
MIR17HG（rs4284505）变体在杂合子（A/G 与 A/A；比值比 [OR] = 0.10，95%置信区间 [CI] = 0.05-0.20，P < 0.001）和显性（A/G+G/G 与 A/A；OR = 0.39，95%CI = 0.25-0.61，P < 0.001）模型下对 SLE 的发病具有保护作用。即使在狼疮肾炎分层的 SLE 中，这种关联仍然一致。相反，rs4284505（G/G）基因型增加了 SLE 的易感性（G/G 与 A/A+A/G；OR = 2.15，95%CI = 1.31-3.53，P = 0.002）。此外，rs4284505 变体与黏膜皮肤病变和 SLEDAI 评分呈显著统计学关联（均 P < 0.05）。
本研究首次探讨了 MIR17HG rs4284505 与 SLE 风险相关；（A/G）基因型具有保护作用，而（G/G）基因型增加了 SLE 的易感性，并与研究人群的疾病严重程度相关。
