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. 2022 Apr 29;11(9):2492.
doi: 10.3390/jcm11092492.

Actual Associations between HLA Haplotype and Graves' Disease Development

Katarzyna Zawadzka-Starczewska  1 , Bogusław Tymoniuk  2 , Bartłomiej Stasiak  3 , Andrzej Lewiński  1   4 , Magdalena Stasiak  1
Affiliations

Actual Associations between HLA Haplotype and Graves' Disease Development

Katarzyna Zawadzka-Starczewska et al. J Clin Med. .

Abstract

The association between HLA and the risk of Graves' disease (GD) has been analyzed for many years. However, the results were often inconsistent and mostly regarded Asian populations. The purpose of our study was to perform HLA genotyping using a next-generation sequencing (NGS) method in Caucasians, to find out which alleles are eventually correlated with GD morbidity as well as which of them can be considered protective. HLA-A, -B, -C, -DQB1, -DRB1 were genotyped using a next-generation sequencing method in 2376 persons, including 159 GD patients and 2217 healthy controls. We have demonstrated a significant association between the risk of GD and the following alleles: HLA-B*08:01, -B*39:06, -B*37:01, -C*07:01, -C*14:02, -C*03:02, -C*17:01, -DRB1*03:01, -DRB1*11:01, -DRB1*13:03, -DRB1*01:03, -DRB1*14:01, -DQB1*03:01, DQB1*02:01. The alleles HLA-B*39:06, -B*37:01, -C*14:02, -C*03:02, -C*17:01, -DRB1*14:01 are novel GD-associated, previously not-reported independent ones with no linkage disequilibrium with other high-risk alleles. On the other hand, the frequencies of HLA-B*07:02, -C*07:02, -C*03:04, DRB1*07:01, -DQB1*02:02, -DQB1*03:03 were significantly lower in GD compared to controls. This study demonstrated the actual relationships between HLA and GD based on the NGS method and provided a novel set of alleles as a reliable tool for an individual personalized risk assessment.

Keywords: Graves’ disease; HLA; human leukocyte antigen; susceptibility alleles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Frequencies (%) of human leukocyte antigen (HLA) over-represented alleles with statistically significant difference between control (open bars) and Graves’ disease (GD) patients (solid bars) for major histocompatibility complex (MHC) class I alleles: HLA-B (a) and HLA-C (b).
Figure 2
Figure 2
Frequencies (%) of human leukocyte antigen (HLA_ over-represented alleles with statistically significant difference between control (open bars) and Graves’ disease (GD) patients (solid bars) for major histocompatibility complex (MHC) class II alleles: HLA-DRB1 (a) and HLA-DQB1 (b).
Figure 3
Figure 3
Frequencies (%) of human leukocyte antigen (HLA) under-represented alleles with statistical difference between controls (open bars) and Graves’ disease (GD) patients (solid bars) for both major histocompatibility complex (MHC) class I and class II alleles.
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