Association of MICA gene polymorphisms with thionamide-induced agranulocytosis



Thionamide-induced agranulocytosis (TIA), namely antithyroid drug (ATD)-induced agranulocytosis, is one of the most feared adverse effect of ATDs. It is defined as a granulocyte count of less than 0.5 × 109/L after ATD administration. Several studies reported that TIA is associated with human leukocyte antigen (HLA) and nearby genes. Our previous study found that the susceptibility genes of TIA are similar in north China and European populations.


We evaluated the associations of 23 candidate single nucleotide polymorphisms (SNPs) in 37 patients with TIA and 254 patients with Graves’ disease (GD) as controls by iPLEX MassARRAY system.


Five SNPs in the MHC class I polypeptide-related sequence A(MICA) genes [rs4349859 (p = 1.43E-7); rs145575084 (p = 5.79E-6); rs116135464 (p = 3.70E-5); rs148015908 (p = 3.79E-5) and rs189600525 (p = 2.15E-4)] were found to be significantly associated with TIA after Bonferroni correction. After combining with previous data of rs4349859 and HLA-B*27:05, the haplotype analysis showed that patients carrying P-A-C-A-T-T-A haplotype have a higher risk of TIA (p = 9.76E-7; OR = 14.85, 95% CI 3.63–60.77).


Our findings suggest that five high linked SNPs of MICA gene are significantly associated with susceptibility to TIA.

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This work was supported by National Key R&D Program of China (2018YFC1314800); Shaanxi Provincial Natural Science Foundation of China (2017JQ8010; 2017SF-171); National Natural Science Foundation of China (No.31301949); the Fundamental Research Funds for the Central Universities (xjj2017135).

Author information




PM designed and performed the experiment under the supervision of YH, and BZ. PM analyzed the data and wrote the main manuscript text under the supervision of YH, JL and BZ. PC, SL, JY collected the samples. JG, HG and XY participated in the experiment. All authors have contributed to the scientific discussion and reviewed the whole manuscript.

Corresponding authors

Correspondence to B. Zhang or Y. He.

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The authors declare no competing financial interests.

Ethical approval

This study was approved by the Medical ethics committee of the First Ailiated Hospital of Xi’an Jiaotong University (ethical approval no. KYLLSL-2013-107-01). All experimental procedures were performed according to standard guidelines and procedures approved by the above Ethics Committee.

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Informed consent was obtained from all participants.

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Ma, P., Chen, P., Gao, J. et al. Association of MICA gene polymorphisms with thionamide-induced agranulocytosis. J Endocrinol Invest 44, 363–369 (2021).

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  • Thionamide-induced agranulocytosis
  • MICA
  • Graves’ disease
  • Association