Biochemical Analysis and Association of Butyrylcholinesterase SNPs rs3495 and rs1803274 with Substance Abuse Disorder.

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.