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Exp Clin Endocrinol Diabetes 2024; 132(01): 17-22
DOI: 10.1055/a-2206-2242
Article

Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis

Yayi He
1   Department of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
,
Pan Ma
2   College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
3   Kunming Center for Medical Service Quality Assessment, Kunming, China
,
Yuanlin Luo
1   Department of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
,
Xiaojuan Gong
2   College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
,
Jiayang Gao
2   College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
,
Yuxin Sun
2   College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
,
Pu Chen
1   Department of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
,
Suliang Zhang
2   College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
,
Yuxin Tian
2   College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
,
Bingyin Shi
1   Department of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
,
Bao Zhang
2   College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
› Author Affiliations 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
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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 - association

Additional material



Publication History

Received: 19 June 2023
Received: 04 October 2023

Accepted: 30 October 2023

Article published online:
18 January 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
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