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阿片类药物使用者中两个基因的启动子甲基化

Promoter Methylation of Two and Genes in Opium Users.

作者信息

Mahmoodi Majid, Karami Fatemeh, Abdollahi Hamidreza, Giahi Navidreza, Divsalar Kouros, Honarmand Amin, Modarressi Mohammad Hossein

机构信息

Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Addict Health. 2023 Apr;15(2):87-92. doi: 10.34172/ahj.2023.1356. Epub 2023 Apr 29.

Abstract

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 and genes. Obtained data were analyzed using SPSS software.

FINDINGS

and genes were found to be significantly methylated in addicted users compared to controls (<0.001) which was significantly associated with the mean of the age regarding gene (=0.002). Neither opium amount nor duration or route of using was associated with the methylation status of or genes.

CONCLUSION

Hypermethylation of and 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.

摘要

背景

阿片类药物滥用在全球范围内急剧增加,尤其是在伊朗。由于阿片类药物的使用与多种人类癌症和神经疾病相关,探寻鸦片的遗传和表观遗传效应可为成瘾者主要健康缺陷的早期诊断铺平道路。因此,本研究旨在确定两个积极参与神经发育和癌症演变的基因启动子的甲基化状态。

方法

从28名阿片类药物滥用者和19名健康对照者的外周血中分离DNA,然后进行超声处理。使用针对 和 基因设计的特异性引物对,对超声处理后的DNA进行甲基化DNA免疫沉淀-实时聚合酶链反应(MeDIP-实时PCR)。使用SPSS软件分析获得的数据。

结果

与对照组相比,成瘾者的 和 基因被发现存在显著甲基化(<0.001),这与 基因的年龄均值显著相关(=0.002)。鸦片用量、使用持续时间或使用途径均与 或 基因的甲基化状态无关。

结论

在阿片成瘾个体中,作为肿瘤抑制基因的 和 基因的高甲基化可被视为鸦片致癌的确证。需要进一步研究以弄清楚表观遗传改变在阿片使用者癌症演变中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0281/10408764/7e62b9e6fab3/ahj-15-87-g001.jpg

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