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DOI: 10.1055/a-2206-2242
Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis
Fundings Institutional foundation of The First Affiliated Hospital of Xi’an Jiaotong University — 2020QN-23 The National Natural Science Foundation of China (82300882) The General project, Shaanxi Science and Technology Research and Development Program — 2022SF-103
Abstract
Objective Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves’ disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA.
Methods Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases.
Results A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09–2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737–18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00–6570.00) d vs. 1080.00 (30.00–3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00–75.00) d vs. 57.50 (21.00–240.00) d, p=0.023).
Conclusions The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.
Key words
KLRC4-KLRK1 - antithyroid drug - induced agranulocytosis - natural killer group 2D - Graves’ disease - associationPublication History
Received: 19 June 2023
Received: 04 October 2023
Accepted: 30 October 2023
Article published online:
18 January 2024
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