Department of Biology, University Campus2, University of Guilan, Rasht, Iran.
Department of Biology, Faculty of sciences, University of Guilan, Rasht, Iran.
Immunol Invest. 2022 Aug;51(6):1908-1919. doi: 10.1080/08820139.2022.2079419. Epub 2022 Jun 28.
Type 1 diabetes (T1DM) is an autoimmune disorder with multiple genetic and environmental risk factors that are still poorly understood. The signal transducer and activator of transcription (STAT) proteins play a pivotal role in immune-cell genesis and regulation. This study aimed to determine the effect of rs1053005 single nucleotide polymorphism (SNP) in 3'-UTR of STAT3 mRNA on the susceptibility to T1DM in an Iranian population.
PCR-RFLP was conducted on 250 T1DM patients and 250 control cases to assess rs1053005 polymorphism. Moreover, several bioinformatics tools were employed to identify the candidate miRNAs targeting the STAT3 mRNA region under study as well as the effect of rs1053005 on their binding site.
Significant variations in the distribution of genotypes and alleles were seen between cases and controls. The comparison results of the frequency of AA, AG, and GG genotypes between T1DM patients and control groups were 49.2% versus 64.8%, 39.2 versus 30%, and 11.6 versus 5.2%, respectively. Individuals who carried GG genotype were at 2.93-fold increased risk of developing T1DM and the G allele was associated with 1.79-fold higher T1DM risk. Bioinformatics analysis demonstrated that due to rs1053005, the interaction of 3 miRNAs were broken, 3 were weakened, 2 were reinforced, and 4 binding sites were created.
The result of this study indicates an association between rs1053005 and T1DM susceptibility which may be due to interference of the SNP with native-binding site of some predicted miRNAs.
1 型糖尿病（T1DM）是一种自身免疫性疾病，具有多种遗传和环境风险因素，但目前仍了解甚少。信号转导和转录激活因子（STAT）蛋白在免疫细胞的发生和调节中起着关键作用。本研究旨在确定 STAT3 mRNA 3'-UTR 中的 rs1053005 单核苷酸多态性（SNP）对伊朗人群 T1DM 易感性的影响。
对 250 例 T1DM 患者和 250 例对照进行 PCR-RFLP 分析，以评估 rs1053005 多态性。此外，还使用了几种生物信息学工具来确定针对所研究的 STAT3 mRNA 区域的候选 miRNA，并研究 rs1053005 对其结合位点的影响。
病例组和对照组在基因型和等位基因的分布上存在显著差异。T1DM 患者和对照组 AA、AG 和 GG 基因型的频率分别为 49.2%比 64.8%、39.2%比 30%和 11.6%比 5.2%。携带 GG 基因型的个体发生 T1DM 的风险增加 2.93 倍，G 等位基因与 T1DM 风险增加 1.79 倍相关。生物信息学分析表明，由于 rs1053005，3 个 miRNA 的相互作用被打破，3 个被削弱，2 个被加强，4 个结合位点被创建。
本研究结果表明，rs1053005 与 T1DM 易感性相关，这可能是由于 SNP 干扰了一些预测 miRNA 的天然结合位点。
