Abstract
Mounting evidence shows that drug dependence involves the complex interplay between genetics and the environment. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) synthesis, which plays an essential role in the development of drug addiction. Noradrenergic dysfunction due to abnormalities TH expression has been implicated in the pathogenesis of drug addiction. We profiled thirteen single-nucleotide polymorphisms (SNPs) and one VNTR (TCAT repeat, UniSTS:240,639) in 512 cases and 600 healthy Chinese subjects to evaluate the relationship between common variants within the TH gene and opioids dependence (OD) in the Chinese Han population. The single-marker analysis determined that rs10770141 (p < 0.001, OR 1.739, 95% CI 1.302 − 2.323) and rs10770140 (p = 0.002, OR 1.536, 95% CI 1.164 − 2.026) are risk variants for OD. The haplotype-association analyses determined that A–C–C–C was a risk factor (p = 0.006, OR 1.662, 95% CI 1.241 − 2.225) for OD. We also observed a significant association between (TACT)9/9 and the duration of transition from the first time using opioids to the development of opioid dependence (DTFUD) (p = 0.002, OR 2.153, 95% CI 1.319 − 3.513). Taken together, this study suggests that TH gene polymorphisms may contribute to the risk of OD in the Chinese Han population.
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Acknowledgements
The authors thank Mr. Yi-chong Wen for data analysis and critical reading of the manuscript and excellent editorial assistance. This work was supported by the Natural Science Foundation of Shaanxi Province (2017JQ8010) and National Natural Science Foundation of China (NSFC81971792).
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The author is indebted to Bao Zhang and Chun-xia Yan for conception, design, funding acquisition, and general supervision of the research group; Jun-lin Liu and Shao-qing Li for gene polymorphism selection, genotyping, drafting, and revising the article; Feng Zhu for acquisition of samples, phenotype definition, and classification; Yu-xiang Zhang for English-polishing of this manuscript and revising it critically for important intellectual content; Ya-nan Wu and Jing-si Yang for analysis and interpretation of data.
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Liu, Jl., Li, Sq., Zhu, F. et al. Tyrosine Hydroxylase Gene Polymorphisms Contribute to Opioid Dependence and Addiction by Affecting Promoter Region Function. Neuromol Med 22, 391–400 (2020). https://doi.org/10.1007/s12017-020-08597-0
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DOI: https://doi.org/10.1007/s12017-020-08597-0