Genetic factors may be involved in disease risk of early-onset autoimmune thyroid disease

Panayiota Siskos ’23

Figure 1: Human leukocyte antigen alleles have been observed to possibly play a genetic role in the risk of early-onset autoimmune thyroid disease.

Autoimmune thyroid diseases, such as Graves’ disease and Hashimoto’s disease, are often characterized by the infiltration of T cells and B cells in the thyroid as well as the production of antibodies specific to thyroid antigens. Genes including human leukocyte antigen (HLA), cytotoxic T lymphocyte-associated factor 4 (CTLA-4), CD40, and protein tyrosine phosphatase-22 (PTPN-22) have been previously associated with susceptibility to autoimmune thyroid diseases. Genetic vulnerability is a great concern for early-onset autoimmune thyroid diseases, and a prior study found that HLA-B*46, -DRB1*08, and -Cw*01 are susceptible alleles of early-onset autoimmune thyroid diseases. Recent studies on the association of HLA with autoimmune disease have focused on investigating  the molecular structure of HLA. Researchers from Catholic University of Korea conducted a study that identified associations of HLA class I and II alleles and amino acid variants with early-onset autoimmune thyroid diseases. The study also investigated whether there are differences in HLA associations between Graves’ disease and Hashimoto’s disease.

The study involved 116 pediatric patients diagnosed with Graves’ disease or Hashimoto’s disease at St. Mary’s Hospital in Seoul from March 2009 to February 2018 with a control group of 142 unrelated healthy Korean adults. Genomic DNA extracted was utilized as a PCR template for genotyping, and consequently 18 alleles for HLA-A, 38 for HLA-B, 21 for HLA-C, 29 for HLA-DRB1, 15 for HLA-DQB1, and 13 for HLA-DPB1 were detected. 

Analysis of associations of HLA class I and II alleles in the patients  revealed that the alleles HLA-B*46:01, -C*01:02, -DPB1*05:01, and -DPB1*02:02 are positively associated with Graves’ disease, while HLA-A*02:07 and -DPB1*02:02 are positively associated with Hashimoto’s disease. The allele HLA-DPB1*05:01 was observed in a  higher frequency in patients that had Graves’ disease than those with Hashimoto’s disease. Differences in distribution of HLA-B*54:01 and -C*03:03 were seen in patients with and without Thyroid associated ophthalmopathy, a disorder related to Graves’ disease. The analysis of amino acid variants showed Leu35 and Glu55 of the HLA-DPB1 had strong associations with Graves’ disease and had different distributions for Graves’ disease and Hashimoto’s disease, respectively.

This research is invaluable for better understanding Graves’ disease and Hashimoto’s disease and the role that genetics plays in the disease risk for early-onset autoimmune thyroid disease. Future steps for this research could involve  directly comparing the genes and alleles of patients with late-onset and early-onset autoimmune thyroid disease, respectively, in order to further elucidate the impact of genetics on autoimmune thyoird disease.

Works Cited:

[1] D. Shin, et al., HLA alleles, especially amino-acid signatures of HLA-DPB1, might contribute to the molecular pathogenesis of early-onset autoimmune thyroid disease. Plos One 14, 2019. doi:

[2] Image retrieved from:



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