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Cellular and Molecular Neurobiology

, Volume 39, Issue 1, pp 137–147 | Cite as

Rs7219 Regulates the Expression of GRB2 by Affecting miR-1288-Mediated Inhibition and Contributes to the Risk of Schizophrenia in the Chinese Han Population

  • Jialei Yang
  • Xiaojing Guo
  • Lulu Zhu
  • Jiao Huang
  • Jianxiong Long
  • Qiang Chen
  • Runde Pan
  • Zhaoxia Chen
  • Xulong Wu
  • Li SuEmail author
Original Research
  • 79 Downloads

Abstract

In the present study, we examined a potential genetic association between the variant rs7219 within the 3′-UTR of GRB2 and the susceptibility to schizophrenia (SCZ) and bipolar disorder (BD) in the Chinese Han population. A genetic association study, including 548 SCZ patients, 512 BD patients, and 598 normal controls, was conducted in the Chinese Han population. Genotyping was performed through the Sequenom MassARRAY technology platform. The expression of GRB2 was detected using quantitative real-time polymerase chain reaction (qRT-PCR). A dual-luciferase reporter assay was performed to determine whether miR-1288 could bind to the 3′-UTR region of GRB2 containing rs7219. We found that rs7219 was significantly associated with the susceptibility to SCZ under different genetic models, including additive [OR (95% CI) = 1.24 (1.02–1.49), P = 0.027], dominant [OR (95% CI) = 1.31 (1.04–1.66), P = 0.025], and allelic models[OR (95% CI) = 1.24 (1.03–1.49), P = 0.027]. However, no significant associations were found between rs7219 and the risk for BD (all P > 0.05). Moreover, we observed that the expression of GRB2 significantly decreased in SCZ patients compared with the controls (P = 0.004). The dual-luciferase reporter assay showed that the minor allele C of rs7219 significantly decreased the luciferase activity by binding miR-1288 (P < 0.001). In summary, we are the first to reveal that rs7219 is significantly associated with the susceptibility to SCZ in the Chinese Han population. Moreover, the minor allele C of rs7219 is identified as a risk allele for SCZ because it generates a binding site for miR-1288, thereby resulting in decreased expression of GRB2 and ultimately increasing the risk of SCZ.

Keywords

Rs7219 GRB2 Dual-luciferase reporter assay Schizophrenia Bipolar disorder 

Notes

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 81460518 and 81573756) and the Science and Technology Program of Guangxi Colleges and Universities (KY2015YB062).

Author Contribution

Li Su designed the study protocol and conceived the framework of this article. Jialei Yang, Jiao Huang, Qiang Chen, and Runde Pan collected the study samples. Jialei Yang, Xiaojing Guo, Lulu Zhu, Jiao Huang, Zhaoxia Chen, and Xulong Wu performed experiments. Jiao Huang, Jianxiong Long, Zhaoxia Chen, and Xulong Wu undertook the statistical analysis. Jialei Yang, Xiaojing Guo, and Lulu Zhu wrote the first draft of this manuscript. All authors contributed to and have approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

All of authors declare that they have no financial or other conflict of interests.

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Authors and Affiliations

  1. 1.School of Public Health of Guangxi Medical UniversityNanningChina
  2. 2.The Guangxi Zhuang Autonomous Region Brain HospitalLiuzhouChina

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