2001-LB: Small RNA-seq Identifies Distinct miRNAs Involved in Familial and Sporadic Type 1 Diabetes Cases from Kuwait

Clinical diagnosis of Type 1 Diabetes (T1D) has been hallmarked by the presence of serum biomarkers such as circulating autoantibodies and c-peptide; however, identification of additional biomarkers associated with T1D is crucial for better diagnosis of the disease and for developing effective therapeutic strategies. Epigenetic modifications, such as dysregulated expression of miRNAs, have also been shown to have a major impact on diabetes and related metabolic complications. In the present study, we aimed to identify the key miRNAs involved in T1D by screening familial and sporadic cases using Next-generation sequencing (NGS) methodology, followed by quantitative real time PCR. The major questions addressed in this study include, what are the key microRNAs, their target genes and molecular pathways involved in T1D. Blood samples were collected from a total of eight families consisting of 18 people with T1D and 18 unaffected first-degree relatives and tested by NGS, followed by validation of key markers in a cohort of 110 sporadic T1D cases and 15 controls without T1D. Our study highlights 23 miRNAs that are differentially expressed in individuals with T1D compared to controls. Functional enrichment analysis of differentially expressed miRNAs highlighted PI3K-AKT as one of the key pathways involved in T1D. We validated the highest order network motif comprising miRNA, key transcription factors and the key miRNA target genes using quantitative real time PCR. Our study portrays hsa-miR-320a, CAV1, GSK3B and MYC as novel transcriptional biomarkers with diagnostic potential for T1D and may lay the foundation for further in-depth research catering better outcome and treatment of T1D.