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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  STAT3  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  STAT3  rs1053005 and T1DM susceptibility which may be due to interference of the SNP with native-binding site of some predicted miRNAs.

The Impact of STAT3 rs1053005 Variation on Type 1 Diabetes Mellitus Susceptibility: Association Study and in Silico Analysis