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miRNA-17-92a-1 宿主基因(MIR17HG)表达特征与 rs4284505 变体在斑秃中的关联:一项病例对照研究。

MicroRNA-17-92a-1 Host Gene (MIR17HG) Expression Signature and rs4284505 Variant Association with Alopecia Areata: A Case-Control Study.

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.

Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA.

出版信息

Genes (Basel). 2022 Mar 12;13(3):505. doi: 10.3390/genes13030505.

Abstract

Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicle immunobiology. We evaluated, for the first time, the miR-17-92a-1 cluster host gene (MIR17HG) expression in peripheral blood of 248 unrelated alopecia areata (AA) patients compared to 244 matched controls using Real-Time qPCR. We also tested its association with different rs4284505A>G genotypes (based on TaqMan allelic discrimination PCR) and the available clinical data. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated for each genetic association model. The upregulation of miR-17 was observed in the serum of patients with alopecia compared to controls (p-value = 0.004). The ROC curve showed high diagnostic performance of miR-17 in differentiating between patients and controls (AUC = 0.85, p-value < 0.001). rs4284505A/G heterozygotes were more susceptible to the disease (OR = 1.57, 95% CI = 1.01−2.45) under the over-dominant model. Interestingly, patients with the rs4284505G/G genotype had a higher level of miR-17 than those with the A/A and A/G genotypes. The G/G genotype was associated with the severe phenotype (p-value = 0.038). A/G carriers were the youngest (p-value < 0.001), had more frequent scalp infection (p-value = 0.006), exhibited the worst dermatology life quality index score (p-value = 0.037), and responded less to treatment (p-value = 0.033). In conclusion, MIR17HG expression and the rs4284505 variant were significantly associated with AA and could play a role in pathogenesis and phenotype in the Egyptian population. Further multi-center studies in other ethnicities are warranted to replicate the findings.

摘要

越来越多的证据表明 microRNAs(miRs)在皮肤和毛囊免疫生物学中的作用。我们首次使用实时 qPCR 评估了 248 例无相关性的斑秃(AA)患者与 244 例匹配对照的外周血中 miR-17-92a-1 簇宿主基因(MIR17HG)的表达。我们还测试了其与不同 rs4284505A>G 基因型(基于 TaqMan 等位基因区分 PCR)的关联,并分析了与可用临床数据的关系。对于每种遗传关联模型,计算了调整后的比值比(OR)和 95%置信区间(CI)。与对照组相比,脱发患者的血清中 miR-17 上调(p 值=0.004)。ROC 曲线显示 miR-17 对区分患者和对照组具有较高的诊断性能(AUC=0.85,p 值<0.001)。在超显性模型下,rs4284505A/G 杂合子更易患该病(OR=1.57,95%CI=1.01-2.45)。有趣的是,rs4284505G/G 基因型的患者的 miR-17 水平高于 A/A 和 A/G 基因型的患者。G/G 基因型与严重的表型有关(p 值=0.038)。A/G 携带者最年轻(p 值<0.001),头皮感染更频繁(p 值=0.006),皮肤病生活质量指数评分最差(p 值=0.037),对治疗的反应性最差(p 值=0.033)。总之,MIR17HG 的表达和 rs4284505 变体与 AA 显著相关,可能在埃及人群的发病机制和表型中起作用。需要在其他种族中进行更多的多中心研究来复制这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf8/8955921/c437774ec0bf/genes-13-00505-g001.jpg

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