Biological Trace Element Research

, Volume 186, Issue 1, pp 85–90 | Cite as

Association of TSHR Gene Copy Number Variation with TSH Abnormalities

  • Yi Pang
  • Yunfeng Guan
  • Xing Jin
  • Hongmei ShenEmail author
  • Lixiang Liu
  • Qingzhen Jia
  • Fangang Meng
  • Xiaoye Zhang


Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland and promotes thyroid growth and function, with increased TSH levels typically associated with hypothyroidism. By consulting the literature, we found that the TSHR, PAX8, and PDE4B genes are associated with thyroid function. Recently, copy number variations (CNVs) have been used as genetic markers to investigate inter-individual variation. Therefore, we investigated the relationship between the TSHR, PAX8, and PDE4B gene CNVs and TSH abnormalities, by calculating variations in gene copy number. Four hundred and eighty-one participants, 232 healthy controls and 249 patients with TSH abnormalities, were selected from three distinct areas in China with different iodine statuses. RT-PCR was used to detect CNVs. Urinary iodine concentrations (UIC) were measured by As3+–Ce4+ catalytic spectrophotometry. There was an association between a CNV at the TSHR gene and TSH abnormalities (p = 0.002). The distribution of PAX8 and PDE4B gene CNVs between patients with TSH abnormalities and healthy controls was not significantly different. UIC > 200 μg/l (OR = 1.49, 95% CI = 1.01–2.22) and the TSHR gene (OR = 6.01, 95% CI = 1.96–18.41) were found to be risk factors for TSH abnormalities. PAX8 and PDE4B gene CNVs were not significantly associated with TSH abnormalities. There was no significant interaction between UIC and any of the examined CNVs. In conclusion, the TSHR gene CNV was associated with the development of TSH abnormalities. No significant associations were revealed between urinary iodine levels and candidate gene CNVs.


TSH abnormalities Copy number variation TSHR PAX8 PDE4B 



We are grateful for the assistance by the Institute for Prevention and Treatment of Endemic Disease of Shanxi Province. And we also thank the colleagues who took part in the survey for their dedication and support.

Authors’ Contribution

The contribution of each author is as follows: Hongmei Shen and Yi Pang designed the research; Yi Pang, Yunfeng Guan, Xing Jin, Hongmei Shen, Lixiang Liu, Qingzhen Jia, Fangang Meng, and Xiaoye Zhang conducted the research; Yi Pang analyzed the data and wrote the paper; Hongmei Shen had primary responsibility for the final content. All authors read and approved the final manuscript.


This study was funded by the National Natural Science Foundation of China (Grant No. 81573098).

Compliance with Ethical Standards

All the procedures used in this experiment were reviewed and approved by the biomedical research ethics committee of Harbin Medical University.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory of Etiology and Epidemiology, National Health and Family Planning Commission, Center for Endemic Disease Control, Chinese Center for Disease Control and PreventionHarbin Medical UniversityHarbinChina
  2. 2.Institute for Endemic Disease Prevention and Treatment of Shanxi ProvinceLinfenChina

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