Type 1 Diabetes and Autoimmune Thyroid Disease—The Genetic Link

Abstract

Type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) are the most frequent chronic autoimmune diseases worldwide. Several autoimmune endocrine and non-endocrine disorders tend to occur together. T1D and AITD often cluster in individuals and families, seen in the formation of autoimmune polyendocrinopathy (AP). The close relationship between these two diseases is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and DQ8 (DQA1*0301-DQB1*0302), tightly linked with DR3 and DR4, are the major common genetic predisposition. Moreover, functional single nucleotide polymorphisms (or rare variants) of various genes, such as the cytotoxic T-lymphocyte- associated antigen (CTLA4), the protein tyrosine phosphatase non-receptor type 22 (PTPN22), the interleukin-2 Receptor (IL2Ra), the Vitamin D receptor (VDR), and the tumor-necrosis-factor-α (TNF) that are involved in immune regulation have been identified to confer susceptibility to both T1D and AITD. Other genes including cluster of differentiation 40 (CD40), the forkhead box P3 (FOXP3), the MHC Class I Polypeptide-Related Sequence A (MICA), insulin variable number of tandem repeats (INS-VNTR), the C-Type Lectin Domain Containing 16A (CLEC16A), the Erb-B2 Receptor Tyrosine Kinase 3 (ERBB3) gene, the interferon-induced helicase C domain-containing protein 1 (IFIH1), and various cytokine genes are also under suspicion to increase susceptibility to T1D and AITD. Further, BTB domain and CNC homolog 2 (BACH2), C-C motif chemokine receptor 5 (CCR5), SH2B adaptor protein 3 (SH2B3), and Rac family small GTPase 2 (RAC2) are found to be associated with T1D and AITD by various independent genome wide association studies and overlap in our list, indicating a strong common genetic link for T1D and AITD. As several susceptibility genes and environmental factors contribute to the disease aetiology of both T1D and AITD and/or AP subtype III variant (T1D+AITD) simultaneously, all patients with T1D should be screened for AITD, and vice versa.

Identification of lncRNA and mRNA Expression Profile in Relapsed Graves’ Disease

“…Although IFIH1, RSAD2, and PARP9 were found to be associated with a variety of autoimmune or inflammatory disease development, such as SLE, RA, Sjögren’s syndrome (SS), type 1 diabetes (T1D), and AITD ( Frommer and Kahaly, 2021 ; Zedan et al, 2021 ), we did not find that these genes were differentially expressed between the recurrent GD group and the normal group. Ubiquitin-specific peptidase 18 (USP18) plays a crucial role in the development of Th17 cells and can regulate the differentiation and function of Treg cells ( Yang et al, 2021 ).…”

Association between miRNA-499 gene polymorphism and autoimmune diseases: A meta-analysis

“…The results suggested a significant association between miRNA-499 rs3746444 polymorphisms and RA risk [ 17 ]. Each autoimmune disease has its characteristics, but recent researches found that some autoimmune diseases share several common mechanisms [ 53 – 55 ], and genetic studies have shown that different autoimmune diseases can largely share the same genetic background [ 56 – 58 ]. People with an autoimmune disease are at risk for another autoimmune disease [ 58 ], and their family members are at increased risk for more than just this autoimmune disease [ 59 , 60 ].…”

Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Hashimoto’s Thyroiditis

“…Interleukin-2 receptor alpha (IL2RA) is one of three subunits that make up the high affinity interleukin 2 receptor (IL-2R) [16]. The IL2RA gene, which is found on chromosome 10p15, encodes CD25 and influences the generation and function of regulatory T cells by acting as a differentiation factor and inhibiting autoreactive T cells in the periphery via CD25 [17]. Beata et al [18] found the rs7093069-IL2RA genotype may increase the risk of autoimmune thyroid diseases.…”