Association of MICA gene polymorphisms with thionamide-induced agranulocytosis

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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

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Fig. 1

Data availability

The authors affirm that all data necessary for confirming the conclusions of the article are present within the article, figures, and tables.

References

  1. 1.

    Weetman AP (2000) Graves' Disease. N Engl J Med 343:1236–1248. https://doi.org/10.1056/NEJM200010263431707

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Ross DS et al (2016) 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26:1343–1421

    Article  Google Scholar 

  3. 3.

    Cooper DS (2005) Antithyroid drugs. N Engl J Med 352:905–917

    CAS  Article  Google Scholar 

  4. 4.

    Watanabe N et al (2012) Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves' disease. J Clin Endocrinol Metab 97:E49–E53

    CAS  Article  Google Scholar 

  5. 5.

    Cheung CL et al (2016) HLA-B* 38: 02: 01 predicts carbimazole/methimazole-induced agranulocytosis. Clin Pharmacol Ther 99:555–561

    CAS  Article  Google Scholar 

  6. 6.

    Nakamura H, Miyauchi A, Miyawaki N, Imagawa J (2013) Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. J Clin Endocrinol Metabol 98:4776–4783

    CAS  Article  Google Scholar 

  7. 7.

    Kobayashi S et al (2014) Characteristics of agranulocytosis as an adverse effect of antithyroid drugs in the second or later course of treatment. Thyroid 24:796–801

    CAS  Article  Google Scholar 

  8. 8.

    Kim HK et al (2015) Characteristics of Korean patients with antithyroid drug-induced agranulocytosis: a multicenter study in Korea. Endocrinol Metabol 30:475–480

    CAS  Article  Google Scholar 

  9. 9.

    Csernok E, Ernst M, Schmitt W, Bainton D, Gross W (1994) Activated neutrophils express proteinase 3 on their plasma membrane in vitro and in vivo. Clin Exp Immunol 95:244–250

    CAS  Article  Google Scholar 

  10. 10.

    Owen CA, Campbell MA, Boukedes SS, Campbell EJ (1995) Inducible binding of bioactive cathepsin G to the cell surface of neutrophils. A novel mechanism for mediating extracellular catalytic activity of cathepsin G. J Immunol 155:5803–5810

    CAS  PubMed  Google Scholar 

  11. 11.

    Vita R, Mazzi V, Antonelli A, Benvenga S (2013) Antithyroid medications and psychosis. Expert Opin Drug Saf 12:865–872

    CAS  Article  Google Scholar 

  12. 12.

    Chen P-L et al (2015) Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Nat Commun 6:7633

    Article  Google Scholar 

  13. 13.

    Thao MP, Tuan PVA, Linh LGH et al (2018) Association of HLA-B∗38:02 with Antithyroid Drug-Induced Agranulocytosis in Kinh Vietnamese Patients. Int J Endocrinol. 2018:7965346

    Article  Google Scholar 

  14. 14.

    He Y et al (2017) Association of HLA-B and HLA-DRB1 polymorphisms with antithyroid drug-induced agranulocytosis in a Han population from northern China. Sci Rep 7:11950

    Article  Google Scholar 

  15. 15.

    Hallberg P et al (2016) Genetic variants associated with antithyroid drug-induced agranulocytosis: a genome-wide association study in a European population. Lancet Diabetes Endocrinol 4:507–516

    CAS  Article  Google Scholar 

  16. 16.

    Zou Y, Stastny P (2010) Role of MICA in the immune response to transplants. Tissue Antigens 76:171–176

    CAS  Article  Google Scholar 

  17. 17.

    Tian W et al (2006) MICA-STR, HLA-B haplotypic diversity and linkage disequilibrium in the Hunan Han population of southern China. Int J Immunogen 33:241–245

    CAS  Article  Google Scholar 

  18. 18.

    Yang J et al (2013) The relationship between bone marrow characteristics and the clinical prognosis of antithyroid drug-induced agranulocytosis. Endocr J 60(2):185–189. https://doi.org/10.1507/endocrj.ej12-0332

    Article  PubMed  Google Scholar 

  19. 19.

    Ostrovsky O et al (2003) NQO2 gene is associated with clozapine induced agranulocytosis. Hum Immunol 10:S140

    Article  Google Scholar 

  20. 20.

    Turbay D et al (1997) Tumor necrosis factor constellation polymorphism and clozapine-induced agranulocytosis in two different ethnic groups. Blood 89:4167–4174

    CAS  Article  Google Scholar 

  21. 21.

    Barrett JC, Fry B, Maller J, Daly MJ (2004) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  Google Scholar 

  22. 22.

    Askar M et al (2017) MHC class I chain-related gene A (MICA) donor-recipient mismatches and MICA-129 polymorphism in unrelated donor hematopoietic cell transplantations has no impact on outcomes in acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndrome: a center for International Blood and Marrow Transplant Research Study. Biol Blood Marrow Transplant 23:436–444

    Article  Google Scholar 

  23. 23.

    Martinez-Borra J et al (2000) HLA-B27 alone rather than B27-related class I haplotypes contributes to ankylosing spondylitis susceptibility. Hum Immunol 61:131–139

    CAS  Article  Google Scholar 

  24. 24.

    Yang H et al (2015) Histone deacetylase inhibitor SAHA epigenetically regulates miR-17–92 cluster and MCM7 to upregulate MICA expression in hepatoma. Br J Cancer 112:112

    CAS  Article  Google Scholar 

  25. 25.

    Yang J et al (2018) Decreased miR-17-92 cluster expression level in serum and granulocytes preceding onset of antithyroid drug-induced agranulocytosis. Endocrine 59:218–225

    CAS  Article  Google Scholar 

  26. 26.

    Pan J et al (2017) Resveratrol promotes MICA/B expression and natural killer cell lysis of breast cancer cells by suppressing c-Myc/miR-17 pathway. Oncotarget 8:65743

    Article  Google Scholar 

Download references

Acknowledgements

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).

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Authors

Contributions

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). https://doi.org/10.1007/s40618-020-01319-0

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Keywords

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