Department of Biosciences, Functional Proteomics and Genomics Lab, COMSATS University Islamabad, Islamabad, Pakistan.
J Mol Neurosci. 2019 Mar;67(3):445-455. doi: 10.1007/s12031-018-1251-7. Epub 2019 Feb 1.
Addiction is a complex mental and behavioral disorder that changes the neurochemistry and physiology of the brain. Genetics also plays a significant role in the pathophysiology of addiction. Butyrylcholinesterase (BChE), a cholinergic enzyme, has been implicated in the metabolism of various drugs, including cocaine, and an association between single-nucleotide polymorphisms (SNPs) of the butyrylcholinesterase gene (BCHE) and neuronal disorders has been reported. We report here the first investigation to be conducted on the status of BChE activity and the potential association of two BCHE gene SNPs, rs3495 (c.*189G > A) and rs1803274 (c.1699G>A, p.Ala567Thr, K-variant), with addiction vulnerability in heroin, hashish and polydrug users. Seventy-five individuals with an addiction to heroin, hashish and/or polydrug use were recruited to this study. BChE levels in the plasma were determined by Ellman's principle. SNPs were genotyped by standard procedures, followed by Sanger sequencing. Plasma BChE levels were found to be significantly higher (p ≤ 0.05) in addicts (mean ± standard error of the mean 0.031 ± 0.004 μmol/L/min; 95% confidence interval [CI] 0.024-0.038) than in non-addicts (controls) (0.014 ± 0.001 μmol/L/min; 95% CI 0.012-0.017). Statistical significant differences were also observed between the addicted cohorts. A statistically significant association for both SNPs (rs3495 and rs1803274) was not observed in addicted subjects tested in the dominant, recessive and allele genetic models, but trends of variations of the rs3495 risk G allele were noted. The authors conclude that BChE plays significant roles in addiction pathophysiology as increased BChE activity in blood samples obtained from the cohorts with addiction was evident. Further studies in this direction may provide novel approaches for the treatment of addiction, but studies with a larger sample size and different ethnic groups are warranted for broader conclusions to be drawn.
成瘾是一种复杂的精神和行为障碍，会改变大脑的神经化学和生理学。遗传学在成瘾的病理生理学中也起着重要作用。丁酰胆碱酯酶（BChE）是一种胆碱能酶，已被涉及各种药物的代谢，包括可卡因，并且已经报道了丁酰胆碱酯酶基因（BCHE）的单核苷酸多态性（SNP）与神经元疾病之间的关联。我们在这里报告首次对 BChE 活性状态以及两个 BCHE 基因 SNP（rs3495（c.*189G > A）和 rs1803274（c.1699G > A，p.Ala567Thr，K-变体））与海洛因、大麻和多药使用者成瘾易感性的潜在关联进行调查。招募了 75 名海洛因、大麻和/或多药使用成瘾者参加本研究。通过 Ellman 原理确定血浆中的 BChE 水平。通过标准程序对 SNP 进行基因分型，然后进行 Sanger 测序。结果发现，成瘾者的血浆 BChE 水平显著升高（p≤0.05）（平均±均值标准误差 0.031±0.004μmol/L/min；95%置信区间 [CI] 0.024-0.038）比非成瘾者（对照组）（0.014±0.001μmol/L/min；95% CI 0.012-0.017）。在成瘾者队列之间也观察到统计学显著差异。在测试的显性、隐性和等位基因遗传模型中，两个 SNP（rs3495 和 rs1803274）均未观察到统计学显著关联，但观察到 rs3495 风险 G 等位基因变异的趋势。作者得出结论，BChE 在成瘾病理生理学中起着重要作用，因为从成瘾队列中获得的血液样本中 BChE 活性增加是明显的。进一步的研究可能为治疗成瘾提供新的方法，但需要更大样本量和不同种族群体的研究来得出更广泛的结论。
