Molecular Genetics and Enzymology Department, Human Genetics and Genome Research Institute, National Research Centre (NRC), 33 El-Buhouth St, Cairo, Egypt.
Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre (NRC), Cairo, Egypt.
Clin Rheumatol. 2024 Aug;43(8):2661-2667. doi: 10.1007/s10067-024-07023-1. Epub 2024 Jun 15.
Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder with wide phenotypic variation that has been observed among individuals who have the same genotype. Modifying genes, epigenetic factors, or environmental factors might all have an impact on genotype-phenotype correlation in FMF. The current research aims to determine the expression levels of microRNAs (miR-148b and miR-17) in Egyptian FMF participants. We also aimed to investigate Caspase -1 gene expression to make a correlation with disease severity. The study comprised 25 clinically diagnosed FMF cases and 25 healthy subjects matched for age and sex. The molecular diagnosis of FMF cases was assessed using real-time SNP genotyping assay. MiR-148b and miR-17 expression were profiled using TaqMan assay technology. The expression level of Caspase -1 gene was also verified using qRT-PCR. MiR-17 in the studied cases was significantly upregulated compared to healthy individuals (P = 0.006), whereas miR-148b was significantly downregulated in the examined patients (P = 0.030). Moreover, statistically significant upregulation of Caspase-1 expression was also elucidated in relation to normal subjects (P = 0.033). The results obtained indicated that miR-17 and miR-148b might be potential regulatory biomarkers in FMF cases. We further hypothesized that the upregulation of Caspase-1 could hint at its significance as a future therapeutic target to alleviate the inflammatory process in these patients. Key Points • The role of miRNAs in FMF and various mechanisms involved in FMF pathogenesis has received increasing attention. • Studying the expression profiles of miR-17 and miR-148b in FMF patients revealed their potential role as regulatory biomarkers in these patients. • Significant upregulation of Caspase-1 expression in FMF cases could hint at its significance as a future therapeutic target. • Future studies on larger cohorts are warranted to clarify and better understand the role of miRNAs in the pathogenesis and severity of FMF.
家族性地中海热（FMF）是一种常染色体隐性遗传性自身炎症性疾病，表型变异广泛，在具有相同基因型的个体中均可观察到。修饰基因、表观遗传因素或环境因素都可能影响 FMF 中的基因型-表型相关性。本研究旨在确定埃及 FMF 参与者中 microRNAs（miR-148b 和 miR-17）的表达水平。我们还旨在研究 Caspase-1 基因的表达，以与疾病严重程度相关联。该研究包括 25 例临床诊断为 FMF 的病例和 25 例年龄和性别匹配的健康对照者。使用实时 SNP 基因分型测定法评估 FMF 病例的分子诊断。使用 TaqMan 分析技术对 miR-148b 和 miR-17 的表达进行了分析。还使用 qRT-PCR 验证了 Caspase-1 基因的表达水平。与健康个体相比，研究病例中的 miR-17 明显上调（P=0.006），而检查患者中的 miR-148b 明显下调（P=0.030）。此外，还阐明了 Caspase-1 表达的统计学显著上调与正常对照者有关（P=0.033）。结果表明，miR-17 和 miR-148b 可能是 FMF 病例中的潜在调节生物标志物。我们进一步假设，Caspase-1 的上调可能暗示其作为减轻这些患者炎症过程的未来治疗靶点的重要性。要点 • miRNA 在 FMF 中的作用及其在 FMF 发病机制中涉及的各种机制已受到越来越多的关注。 • 研究 FMF 患者中 miR-17 和 miR-148b 的表达谱揭示了它们作为这些患者调节生物标志物的潜在作用。 • FMF 病例中 Caspase-1 表达的显著上调可能暗示其作为未来治疗靶点的重要性。 • 需要对更大的队列进行进一步研究，以阐明和更好地理解 miRNA 在 FMF 的发病机制和严重程度中的作用。
