Eskandarion Mohammad Reza, Jafaripour Simin, Heidari Farid, Talebi Elham, Taleghani Maryam Rezakhani, Maserat Neda, Forutan Maryam, Ghorbani Raheb, Gharehdaghi Jaber, Shirkoohi Reza, Raoofian Reza
Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.
Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Front Psychiatry. 2024 Dec 20;15:1398666. doi: 10.3389/fpsyt.2024.1398666. eCollection 2024.
Glutathione S-transferase (GST) has the ability to detoxify the cellular environment of xenobiotic compounds and by-products of oxidative stress. The expression levels of GST genes and their polymorphisms are associated with various human diseases. Methamphetamine and opiate addiction also account for a significant proportion of SUDs in Iran. Considering the oxidative stress induced by morphine and methamphetamine and the potential of GST as a therapeutic option for SUD, we aimed to investigate the association of common genetic variations of two genes from GST family, GSTT1 and GSTM1, with addiction to morphine and METH in Iranian population.
A total of 160 blood and urine samples were randomly collected from 50 opiums and 30 methamphetamine users and 80 healthy controls. All samples were processed by thin layer chromatography (TLC), high performance liquid chromatography, and Gas Chromatography-Mass Spectrometry (GC-MS) techniques to detect opium alkaloids (morphine, codeine, papaverine, noscapine, etc.), methamphetamine stimulants, and other legal and illegal drugs. The genotypes of GSTM1 and GSTT1 polymorphisms were determined by PCR. Statistical analysis was performed using the SPSS. This project was approved by the Research Ethics Committee of Legal Medicine Organization, Tehran, Iran.
A statistically significant association was observed between the GSTM1 polymorphisms and morphine addiction under a recessive genetic model. The reference group consisted of pooled n/p and p/p genotypes, with an odds ratio (OR) of 2.15, a 95% confidence interval (CI) of 1.05 to 4.39, and a P-value of 0.03. In contrast, there was no statistically significant association between genetic variations in the GSTT1 gene and morphine or methamphetamine addiction. The results revealed no significant association between GSTT1 and GSTM1 allele frequencies and morphine and methamphetamine addiction when divided into risk allele carriers and noncarriers.
These findings suggest that the GSTM1 gene may be involved in the development of morphine addiction. However, further studies with larger sample sizes are required to verify these results and investigate the underlying molecular mechanisms.
谷胱甘肽S-转移酶(GST)具有使细胞环境中的外源性化合物和氧化应激副产物解毒的能力。GST基因的表达水平及其多态性与多种人类疾病相关。甲基苯丙胺和阿片类药物成瘾在伊朗药物滥用障碍(SUDs)中也占很大比例。考虑到吗啡和甲基苯丙胺诱导的氧化应激以及GST作为SUD治疗选择的潜力,我们旨在研究GST家族中两个基因GSTT1和GSTM1的常见基因变异与伊朗人群中吗啡和甲基苯丙胺成瘾的关联。
从50名阿片类药物使用者、30名甲基苯丙胺使用者和80名健康对照中随机收集了总共160份血液和尿液样本。所有样本均通过薄层色谱法(TLC)、高效液相色谱法和气相色谱-质谱联用(GC-MS)技术进行处理,以检测鸦片生物碱(吗啡、可待因、罂粟碱、那可丁等)、甲基苯丙胺兴奋剂以及其他合法和非法药物。通过聚合酶链反应(PCR)确定GSTM1和GSTT1多态性的基因型。使用SPSS进行统计分析。本项目经伊朗德黑兰法医学组织研究伦理委员会批准。
在隐性遗传模型下,观察到GSTM1多态性与吗啡成瘾之间存在统计学显著关联。参照组由合并的n/p和p/p基因型组成,比值比(OR)为2.15,95%置信区间(CI)为1.05至4.39,P值为0.03。相比之下,GSTT1基因的基因变异与吗啡或甲基苯丙胺成瘾之间没有统计学显著关联。结果显示,当分为风险等位基因携带者和非携带者时,GSTT1和GSTM1等位基因频率与吗啡和甲基苯丙胺成瘾之间没有显著关联。
这些发现表明GSTM1基因可能参与吗啡成瘾的发生。然而,需要进一步进行更大样本量的研究来验证这些结果并探究潜在的分子机制。