Abstract

Objectives

Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disorder characterized by recurrent fever and serositis episodes. Identification of low penetrant or heterozygous MEFV mutations in clinically diagnosed FMF patients did raise a concern on whether epigenetic or environmental factors play an additional role in FMF pathogenesis. We aimed to investigate the expression profile of apoptosis-related miRNAs in FMF and their influence on clinical manifestations in the present study.

Method

191 pediatric FMF patients and 31 healthy children included in the study. Expressions of 33 apoptosis-related, circulating cell-free miRNAs were evaluated by a quantitative polymerase chain reaction, statistically calculated within ΔΔCt values and fold changes were evaluated by Welch T test, in which p < 0.05 were considered to be significant.

Results

Nineteen miRNAs, including let-7a-5p, let-7c, let-7 g-5p, miR-15b-5p, miR-16-5p, miR-17-5p, miR-23a-3p, miR-24-3p, miR-25-3p, miR-26a-5p, miR-26b-5p, miR-27a-3p, miR-29c-3p, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR-106b-5p, miR-146a-5p, and miR-195-5p, were found down-regulated; miR-15a-5p, miR-29b-3p, miR-181a-5p, miR-181b-5p, miR-181c-5p, miR-214-3p, and miR-365a-3p were up-regulated in FMF patients. In detail, these miRNAs were similar among FMF patients in terms of genotype, colchicine response, and having an inflammatory attack during analysis.

Conclusion

We found that 26 apoptosis-related circulating miRNAs were deregulated in children with FMF. Thus, we speculate that these miRNAs have a role in FMF pathogenesis via apoptotic mechanisms.

中文翻译：

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家族性地中海热患儿中细胞凋亡相关循环无细胞 miRNA 的表达改变：一项横断面研究

摘要

目标

家族性地中海热 (FMF) 是最常见的遗传性自身炎症性疾病，其特征是反复发烧和浆膜炎发作。在临床诊断的 FMF 患者中识别低外显性或杂合MEFV突变确实引起了人们对表观遗传或环境因素是否在 FMF 发病机制中发挥额外作用的担忧。我们旨在研究 FMF 中凋亡相关 miRNA 的表达谱及其对本研究中临床表现的影响。

方法

该研究包括 191 名儿科 FMF 患者和 31 名健康儿童。通过定量聚合酶链反应评估 33 种细胞凋亡相关的循环无细胞 miRNA 的表达，在 ΔΔCt 值内进行统计计算，并通过 Welch T检验评估倍数变化，其中p  < 0.05 被认为是显着的。

结果

19个miRNA，包括let-7a-5p、let-7c、let-7 g-5p、miR-15b-5p、miR-16-5p、miR-17-5p、miR-23a-3p、miR-24-3p , miR-25-3p, miR-26a-5p, miR-26b-5p, miR-27a-3p, miR-29c-3p, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR -106b-5p、miR-146a-5p 和 miR-195-5p 被发现下调；miR-15a-5p、miR-29b-3p、miR-181a-5p、miR-181b-5p、miR-181c-5p、miR-214-3p和miR-365a-3p在FMF患者中上调。详细地说，这些 miRNA 在 FMF 患者中在基因型、秋水仙碱反应和分析过程中的炎症发作方面是相似的。

结论

我们发现 26 种凋亡相关循环 miRNA 在 FMF 儿童中失调。因此，我们推测这些 miRNA 通过凋亡机制在 FMF 发病机制中起作用。