Bayat Reza, Salehi Zivar, Dalili Setila, Mashayekhi Farhad
Department of Biology, University Campus2 University of Guilan Rasht Iran.
Department of Biology, Faculty of Sciences University of Guilan Rasht Iran.
Health Sci Rep. 2025 Mar 2;8(3):e70480. doi: 10.1002/hsr2.70480. eCollection 2025 Mar.
Alterations in the expression pattern of miRNAs seem to be linked with autoimmune diseases such as type 1 diabetes mellitus (T1DM). Regarding the importance of assessing this potential link, we aimed to evaluate the relationship between single-nucleotide polymorphism (SNP) and T1DM susceptibility. Furthermore, we investigated the expression level in T1DM.
A total of 250 T1DM patients and 250 controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and miR-21 expression levels were assessed using real-time PCR. Moreover, the potential targets of miR-21 were investigated using different bioinformatics web servers.
Our results showed that the T/C genotype and the C allele were more frequent in T1DM patients than in controls. Individuals carrying the T/C genotype in overdominant model were 2.74-fold at a higher risk of T1DM (OR = 2.74; 95%CI, 1.78-4.27; < 0.0001). In addition, miR-21 expression was more than twofold higher in patients than in controls ( < 0.0001) and it was found to be significantly upregulated when carrying the T/C genotype. Regarding miR-21 predicted target genes, its overexpression may be associated with beta cell death, diabetic nephropathy, inflammatory responses, impaired insulin production or secretion, and T-cell cytotoxicity, which are important in the initiation and progression of T1DM.
Our results suggested that miR-21 may confer genetic susceptibility to T1DM. Therefore, it seems that this genetic link should be further investigated to enhance diagnostic and therapeutic strategies in these patients.
微小RNA（miRNA）表达模式的改变似乎与自身免疫性疾病如1型糖尿病（T1DM）有关。鉴于评估这种潜在联系的重要性，我们旨在评估单核苷酸多态性（SNP）与T1DM易感性之间的关系。此外，我们还研究了T1DM中的表达水平。
使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对250例T1DM患者和250例对照进行基因分型，并使用实时PCR评估miR-21的表达水平。此外，使用不同的生物信息学网络服务器研究miR-21的潜在靶标。
我们的结果显示，T/C基因型和C等位基因在T1DM患者中比在对照中更常见。在超显性模型中携带T/C基因型的个体患T1DM的风险高2.74倍（OR = 2.74；95%CI，1.78 - 4.27；P < 0.0001）。此外，患者中miR-21的表达比对照高两倍以上（P < 0.0001），并且发现携带T/C基因型时miR-21表达显著上调。关于miR-21预测的靶基因，其过表达可能与β细胞死亡、糖尿病肾病、炎症反应、胰岛素产生或分泌受损以及T细胞细胞毒性有关，这些在T1DM的发生和发展中很重要。
我们的结果表明，miR-21可能赋予T1DM遗传易感性。因此，似乎应该进一步研究这种遗传联系，以加强对这些患者的诊断和治疗策略。
