Association of HLA class II genes with autoimmune thyroid diseases in children with type 1 diabetes

Human leukocyte antigen (HLA) class II genes are one of the main genetic susceptibility factors of the most common autoimmune diseases, including type 1 diabetes mellitus (T1D) and autoimmune thyroid diseases (AITD). Distinct HLA alleles are associated with autoimmune endocrinopathies in different populations. This work was aimed to reveal the alleles associated with a predisposition to AITD in children with T1D in Belarus. 49 patients with a combination of T1D and AITD (autoimmune polyglandular syndrome type 3a – APS type 3a), 95 patients with T1D and 24 healthy controls were included into the study. HLA typing for 3 genes (DRB1, DQB1, DQА1) was performed by SBT (sequence-based typing) in the children with T1D and APS type 3a and by high-performance sequencing of a new generation (Illumina) in the children of the control group. We identified a number of alleles and haplotypes DRB1, DQB1, DQA1 associated with a predisposition or resistance to both forms of autoimmune pathology (T1D and APS type 3a) in healthy children. These data indicate a common spectrum of polymorphic variants of HLA class II genes involved in the etiopathogenesis of T1D and APS type 3 in the Belarusian population. At the same time, the children with type 3a APS had a higher total frequency of certain HLA-DRB1*04 allele subtypes and one of the variants of the DRB4-DQ4.3 haplotype, compared with the patients with isolated T1D. These revealed genetic markers can be used to identify high-risk groups of AITD in children with T1D in the Belarusian population.

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