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

Yayi He; Pan Ma; Yuanlin Luo; Xiaojuan Gong; Jiayang Gao; Yuxin Sun; Pu Chen; Suliang Zhang; Yuxin Tian; Bingyin Shi; Bao Zhang

doi:10.1055/a-2206-2242

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

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

Authors

Yayi He

¹Department of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Pan Ma

²College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China

³Kunming Center for Medical Service Quality Assessment, Kunming, China
Yuanlin Luo

¹Department of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Xiaojuan Gong

²College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Jiayang Gao

²College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yuxin Sun

²College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Pu Chen

¹Department of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Suliang Zhang

²College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yuxin Tian

²College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Bingyin Shi

¹Department of Endocrinology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
Bao Zhang

²College of Medicine & Forensic, Health Science Center, Xi’an Jiaotong University, Xi’an, China

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

Full Text

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