Department of Pediatrics, Faculty of Medicine, Cukurova University, Adana, Turkey.
Department of Pediatric Rheumatology, Faculty of Medicine, Cukurova University, Adana, Turkey.
Rheumatol Int. 2021 Jan;41(1):103-111. doi: 10.1007/s00296-020-04541-4. Epub 2020 Mar 5.
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.
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.
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.
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.
家族性地中海热（FMF）是最常见的遗传性自身炎症性疾病，其特征为反复发作的发热和浆膜炎发作。在临床诊断为 FMF 的患者中发现低外显率或杂合性 MEFV 突变，这引起了人们的关注，即表观遗传或环境因素是否在 FMF 的发病机制中发挥额外作用。我们旨在研究凋亡相关 miRNA 在 FMF 中的表达谱及其对本研究中临床表现的影响。
纳入 191 例儿科 FMF 患者和 31 例健康儿童。通过定量聚合酶链反应评估 33 种凋亡相关的循环无细胞 miRNA 的表达，在ΔΔCt 值内进行统计学计算，并通过 Welch T 检验评估倍数变化，其中 p<0.05 被认为具有统计学意义。
19 种 miRNA，包括 let-7a-5p、let-7c、let-7g-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。具体而言，在分析过程中，根据基因型、秋水仙碱反应和炎症发作，FMF 患者之间这些 miRNA 相似。
我们发现，26 种与凋亡相关的循环 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 的发病机制中发挥作用。
