Decreased miR-17-92 cluster expression level in serum and granulocytes preceding onset of antithyroid drug-induced agranulocytosis
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We aimed to determine changes in miR-17-92 cluster expression in serum and granulocytes from patients with antithyroid drug (ATD)-induced agranulocytosis.
In this study, real-time polymerase chain reaction (PCR) was used to detect serum miR-17-92 expression levels in 20 ATD-induced agranulocytosis and 16 control patients. Importantly, dynamic changes in neutrophil counts from granulocytopenia to agranulocytosis were observed in 6 of the 20 patients. miR-17-92 expression levels in granulocytes of those six patients under the granulocytopenia condition were measured and compared with corresponding granulocyte samples after recovery. Additionally, the expression levels of these miRNAs in patients with type I or type II bone marrow characteristics were analyzed, and the correlation between miR-17-92 and serum free thyroxine level was analyzed.
We found that levels of miR-17-92 expression decreased in both serum and pre-agranulocytosis granulocytes from patients with ATD-induced agranulocytosis compared with those in serum and granulocytes from both recovered patients and control patients. However, no difference among patients with either type of bone marrow characteristics was observed, and no correlation between serum miR-17-92 and free thyroxine levels was found.
In ATD-induced agranulocytosis, expression of the miR-17-92 cluster is reduced in both serum and granulocytes, though this alteration does not correlate with bone marrow characteristics or thyroid function.
KeywordsAntithyroid drug Agranulocytosis miR-17-92 cluster Granulocytes.
This work was supported by grants from the National Natural Science Foundation of China (No. 81100560) and the Zhengxiang Scholar Program (Prof. Xiangyang Tang) of University of South China. We highly appreciate Dr. Zhenzhong Cui (Ph.D., Senior Staff Scientist of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH) for his careful review of this manuscript. We also thank all the patients for their cooperation in this study.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 6.T.S. Plantinga, P. Arts, G.H. Knarren, A.H. Mulder, I.M. Wakelkamp, A.R. Hermus, L.A. Joosten, M.G. Netea, P.H. Bisschop, W.W. De Herder, H.J. Beijers, I.J. De Bruin, C. Gilissen, J.A. Veltman, A. Hoischen, J.W. Smit, R.T. Netea-Maier, Rare NOX3 variants confer susceptibility to agranulocytosis during thyrostatic treatment of Graves’ disease. Clin. Pharmacol. Thera (2017). https://doi.org/10.1002/cpt.733
- 7.P.L. Chen, S.R. Shih, P.W. Wang, Y.C. Lin, C.C. Chu, J.H. Lin, S.C. Chen, C.C. Chang, T.S. Huang, K.S. Tsai, F.Y. Tseng, C.Y. Wang, J.Y. Lu, W.Y. Chiu, C.C. Chang, Y.H. Chen, Y.T. Chen, C.S. Fann, W.S. Yang, T.C. Chang, Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Nat. Commun. 6, 7633 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
- 8.P. Hallberg, N. Eriksson, L. Ibanez, E. Bondon-Guitton, R. Kreutz, A. Carvajal, M.I. Lucena, E.S. Ponce, M. Molokhia, J. Martin, T. Axelsson, Q.Y. Yue, P.K. Magnusson, M. Wadelius, D.a.C.C. Eu, Genetic variants associated with antithyroid drug-induced agranulocytosis: a genome-wide association study in a European population. Lancet Diabetes Endocrinol. 4, 507–516 (2016)CrossRefPubMedGoogle Scholar
- 19.S. Mi, Z. Li, P. Chen, C. He, D. Cao, A. Elkahloun, J. Lu, L.A. Pelloso, M. Wunderlich, H. Huang, R.T. Luo, M. Sun, M. He, M.B. Neilly, N.J. Zeleznik-Le, M.J. Thirman, J.C. Mulloy, P.P. Liu, J.D. Rowley, J. Chen, Aberrant overexpression and function of the miR-17-92 cluster in MLL-rearranged acute leukemia. Proc. Natl. Acad. Sci. USA 107, 3710–3715 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
- 23.A. Ventura, A.G. Young, M.M. Winslow, L. Lintault, A. Meissner, S.J. Erkeland, J. Newman, R.T. Bronson, D. Crowley, J.R. Stone, R. Jaenisch, P.A. Sharp, T. Jacks, Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132, 875–886 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
- 28.G. Zhang, X. Liu, W. Wang, Y. Cai, S. Li, Q. Chen, M. Liao, M. Zhang, G. Zeng, B. Zhou, C.G. Feng, X. Chen, Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages. Cell. Cycle 15, 2527–2538 (2016)CrossRefPubMedPubMedCentralGoogle Scholar