1486-P: Role of HLA Class I Gene Alleles and Haplotypes in Type 1 Diabetes in Kuwaiti Children

Introduction & Objective: HLA class I genes have a role in influencing immune response and self-tolerance as they bind and present antigens to T cells. Allelic variations of these genes are associated with multifactorial autoimmune conditions including type 1 diabetes (T1D) and show variability across different ethnic groups and populations. Additionally, the amino acid variations of these genes may affect the binding and immunogenicity of insulin peptide. Methods: We performed an association study of classical HLA class I genes between Kuwaiti T1D children (95 individuals) and adult controls (150 individuals) groups using Next-generation sequencing dataset. Results: Significant associations were identified for alleles at HLA-A and HLA-C genes, including A*02:01 and C*07:01 were both conferred high risk for T1D. The A*24:02~B* 08:01~C*07:02 haplotype was significantly associated with the risk of developing T1D. Furthermore, we identified significant 33 amino acid positions at HLA-B and HLA-C genes that were both predisposing and protective against T1D. Conclusion: Our results suggest that HLA class I genes and their allelic and amino acid variations play a role in modulating the risk of T1D and may have implications for disease risk management and genetic counseling in the Kuwaiti population.