Abstract
To study the potential role of brain-derived neurotrophic factor (BDNF) methylation in heroin addiction, we first detected the methylation level of seven CpG islands that included 106 CpG sites in the promoter regions of BDNF from 120 people addicted to heroin and 113 controls. Methylation quantitative trait locus (mQTL) analysis was then employed to determine the association between the single-nucleotide polymorphism rs6265, a well-known locus shown to be correlated with heroin addiction, and the methylation levels of these CpG sites. Finally, we used the JASPAR database to predict whether transcription factors could bind to these CpG sites. We found that the methylation levels of CpG islands 6 and 7 and the methylation levels of BDNF_45 and BDNF_80 were significantly higher in the heroin addiction group than in the control group. We also found that rs6265 was an mQTL and was associated with the methylation level of BDNF_58. Using the JASPAR database, we found that ALX homeobox 3 (ALX3), achaete-scute family bHLH transcription factor 1 (ASCL1) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) could bind to CpG island 6, and ALX3 could bind to CpG island 7. In summary, we showed that increased DNA methylation in the promoter regions of the BDNF gene was associated with heroin addiction in Han Chinese.
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The data and material in this study are available from the corresponding author on reasonable request.
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Acknowledgements
We warmly thank the participants for their contributions.
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This work was supported by the National Natural Science Foundation of China (No. 82004170), and the scientific research project of Shaanxi University of Chinese Medicine (No.2020GP21).
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YL, YZ and YX were responsible for the study concept and design; YZ and YL contributed to the acquisition of samples; YX assisted with data analysis and interpretation of findings; YX drafted the manuscript; YX, YZ and YL provided critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.
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Written informed consent was obtained from all participants. Our study was approved by the Ethical Committee of Xi’an Mental Health Centre. All our experimental operations were performed in accordance with approved guidelines.
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Xiao, Y., Zhu, Y. & Li, Y. Elevation of DNA Methylation in the Promoter Regions of the Brain-Derived Neurotrophic Factor Gene is Associated with Heroin Addiction. J Mol Neurosci 71, 1752–1760 (2021). https://doi.org/10.1007/s12031-021-01864-0
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DOI: https://doi.org/10.1007/s12031-021-01864-0