Abstract
Autoimmune thyroid diseases (AITDs) which include Graves' disease (GD) and Hashimoto's thyroiditis (HT) as well as type 1 diabetes (T1D) are common autoimmune disorders in children. Many genes are involved in the modulation of the immune system and their polymorphisms might predispose to autoimmune diseases development. According to the literature genes encoding IL2RA (alpha subunit of Interleukin 2 receptor), IFIH1 (Interferon induced with helicase C domain 1) and CTLA-4 (cytotoxic T cell antigen 4) might be associated with autoimmune diseases pathogenesis. The aim of the study was to assess the association of chosen single nucleotide polymorphisms (SNPs) of IL2RA, IFIH1, and CTLA-4 genes in the group of Polish children with AITDs and in children with T1D. We analyzed single nucleotide polymorphisms (SNPs) in the IL2RA region (rs7093069), IFIH1 region (rs1990760) and CTLA-4 region (rs231775) in group of Polish children and adolescents with type 1 diabetes (n = 194) and autoimmune thyroid diseases (GD n = 170, HT n = 81) and healthy age and sex matched controls for comparison (n = 110). There were significant differences observed between T1D patients and control group in alleles of IL2RA (rs7093069 T > C) and CTLA-4 (rs231775 G > A). In addition, the study revealed T/T genotype at the IL2RA locus (rs7093069) and G/G genotype at the CTLA-4 locus (rs231775) to be statistically significant more frequent in children with T1D. Moreover, genotypes C/T and T/T at the IFIH1 locus (rs1990760) were significantly more frequent in patients with T1D than in controls. We observed no significant differences between AITD patients and a control group in analyzed SNPs. In conclusion, we detected that each allele T of rs7093069 SNP at the IL2RA locus and G allele of rs231775 SNP at the CTLA-4 locus as well as C/T and T/T genotypes of rs1990760 SNP at the IFIH1 locus are predisposing in terms of T1D development. Thereby, we confirmed that IL2RA, IFIH1, and CTLA-4 gene locus have a role in T1D susceptibility. The analysis of selected SNPs revealed no association with AITDs in a group of Polish children and adolescents.
Highlights
The underlying cause of autoimmune diseases is the loss of immune tolerance to tissue-specific antigenic peptides which leads to immune response directed against one’s own body’s cells
Since it has been suggested that multiple genes are associated with pathogenesis of autoimmune disorders and some autoimmune diseases might share the same genetic background of co-occurrence within individuals and families, the aim of the study was to assess the association of chosen single nucleotide polymorphisms of IL2RA, Interferon induced with helicase C domain 1 (IFIH1), and Cytotoxic T-lymphocyte antigen-4 (CTLA-4) genes in the group of Polish children with autoimmune thyroid diseases (AITDs) and in children with type 1 diabetes (T1D)
Significant associations were observed between T1D patients and controls in alleles of IL2RA (Figure 2) and CTLA-4 (Figure 6)
Summary
The underlying cause of autoimmune diseases is the loss of immune tolerance to tissue-specific antigenic peptides which leads to immune response directed against one’s own body’s cells. Among the most common chronic autoimmune endocrine disorders in children there are autoimmune thyroid diseases (AITDs) which include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) as well as type 1 diabetes (T1D) [2]. In diabetic patients an inappropriate immune reaction results in autoreactive T-cell infiltration and production of tissue specific autoantibodies which cause the destruction and dysfunction of the insulin secreting pancreatic beta cells and insulin deficiency [4]. Recent studies have demonstrated that some genetic risk factors for autoimmunity are shared between diseases, contributing to the development of more than one autoimmune disorder [10]. Certain polymorphic variants of genes encoding IL2AR, CTLA-4, or IFIH1 have been reported to implicate T1D and ATDs development in adults, there are only few studies focusing on children [14,15,16,17,18]
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