Methylation quantitative trait locus rs5326 is associated with susceptibility and effective dosage of methadone maintenance treatment for heroin use disorder

Zhang, Jianbo; Fan, Yijun; Zhou, Jiarong; Ma, Tengfei; Gao, Keqiang; Xu, Min; Xiao, Yifan; Zhu, Yan

doi:10.1007/s00213-021-05968-8

Cited by 5 publications

(2 citation statements)

References 47 publications

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“…With potential role in regulating DNA methylation, mQTLs were believed to constitute more liability than random SNPs in diseases including heroin addiction (J. Zhang et al, 2021). Unfortunately, we failed to detect any association between the risk SNP rs6356 for heroin addiction and the methylation level of TH_15.…”

Section: Discussionmentioning

confidence: 72%

Expression Quantitative Trait Locus rs6356 Is Associated with Susceptibility to Heroin Addiction by Potentially Influencing TH Gene Expression in the Hippocampus and Nucleus Accumbens

Wang

Zhang

et al. 2022

J Mol Neurosci

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Opioid addiction is a complicated and highly heritable brain disease. Dysfunction of dopaminergic signaling is involved in the pathogenesis of addictive disorders. Encoding the synthetase of dopamine, tyrosine hydroxylase (TH) gene has long been an interesting candidate in the genetic association studies for opioid addiction. However, the underlying mechanism of the association of risk gene variants and opioid addiction remains unknown. In the present study, we rst analyzed the association between TH gene variants and susceptibility and traits of heroin addiction in 801 patients with heroin addiction and 930 healthy controls. The methylation level in the promoter region of the TH gene was detected and compared between the heroin addiction and healthy control groups. To reveal the potential mechanism of the association of TH gene variants and heroin addiction, correlation between the risk TH SNPs for heroin addiction and the methylation as well expression level of TH gene were examined. Our results demonstrated that SNP rs6356 was associated with the susceptibility of heroin addiction. CpG TH_15 was hypermethylated in the heroin addiction group compared with the healthy control group. Notably, SNP rs6356 was allele-speci c correlated with the expression of TH gene in the hippocampus and nucleus accumbens, but not the methylation level of CpG TH_15. Our ndings suggest that the eQTL rs6356 was associated with the risk of heroin addiction by potentially affecting the expression of TH gene in the mesocorticolimbic dopamine system brain regions including hippocampus and nucleus accumbens.

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Section: Discussionmentioning

confidence: 72%

Expression Quantitative Trait Locus rs6356 Is Associated with Susceptibility to Heroin Addiction by Potentially Influencing TH Gene Expression in the Hippocampus and Nucleus Accumbens

Wang

Zhang

et al. 2022

J Mol Neurosci

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“…However, the correlations between the methylation of the aforementioned sites and the frequency, amount, and duration of heroin use were not evaluated. 27 In spite of limited studies investigating the role of opium abuse on genome methylation, genetic and epigenetic effects induced by opium and opioid have been extensively studied in various types of human cancer, so that the results may change the future of pain management. 7,28,29 In this regard, finding the hypermethylation of HOXA9 and NISCH, as two potential tumor suppressor genes in the present study, presumably is another evidence of the tumor stimulating effects of opium which can be studied in opium-addicted cancer patients as well.…”

Section: Discussionmentioning

confidence: 99%

Promoter Methylation of Two HOXA9 and NISCH Genes in Opium Users

Mahmoodi,

Karami,

Abdollahi

et al. 2023

Addict Health

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Background: Opiate abuse has been critically increased in the world, especially in Iran. Owing to the association of opiate use with multiple human cancers and neurological disorders, seeking for genetic and epigenetic effects of opium can pave the way for early diagnosis of major health defects in addicted users. Accordingly, the present study aimed to determine the methylation status of the promoter of two genes, which are actively involved in neurodevelopment and cancer evolution. Methods: DNA was isolated from peripheral blood of 28 opium abusers and 19 healthy controls and then subjected to sonication. Sonicated DNAs undergone methylated DNA immunoprecipitation-real time polymerase chain reaction (MeDIP-Real Time PCR) using specific primer pairs designed for HOXA9 and NISCH genes. Obtained data were analyzed using SPSS software. Findings: HOXA9 and NISCH genes were found to be significantly methylated in addicted users compared to controls (P<0.001) which was significantly associated with the mean of the age regarding HOXA9 gene (P=0.002). Neither opium amount nor duration or route of using was associated with the methylation status of HOXA9 or NISCH genes. Conclusion: Hypermethylation of HOXA9 and NISCH genes as tumor suppressor in opium-addicted individuals can be considered as confirmatory evidence for carcinogenesis of opium. Further studies are required to figure out the role of epigenetic alterations in cancer evolution among opium users.

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Methylation and expression quantitative trait locus rs6296 in the HTR1B gene is associated with susceptibility to opioid use disorder

Xie

et al. 2022

Psychopharmacology

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Methylation quantitative trait locus rs5326 is associated with susceptibility and effective dosage of methadone maintenance treatment for heroin use disorder

Cited by 5 publications

References 47 publications

Expression Quantitative Trait Locus rs6356 Is Associated with Susceptibility to Heroin Addiction by Potentially Influencing TH Gene Expression in the Hippocampus and Nucleus Accumbens

Expression Quantitative Trait Locus rs6356 Is Associated with Susceptibility to Heroin Addiction by Potentially Influencing TH Gene Expression in the Hippocampus and Nucleus Accumbens

Promoter Methylation of Two HOXA9 and NISCH Genes in Opium Users

Methylation and expression quantitative trait locus rs6296 in the HTR1B gene is associated with susceptibility to opioid use disorder

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