۱- Introduction

۲- Material and methods

۳- Results

۴- Discussion

۵- Conclusion

References

Abstract

Substance addiction is a chronic, relapsing mental disorder Characterized by compulsive drug seeking, and loss of control over drug intake and relapse after prolonged abstinence. Genetics has been shown to contribute towards an individual’s vulnerability to addiction. Acetylecholine (ACh), a cholinergic neurotransmitter hydrolyzed by acetylcholinesterase (AChE), is an essential neurotransmitter and neuromodulator in central and peripheral nervous system and has regulatory influence on numerous neuronal functions including addiction. The present study was carried out to investigate the role of acetylcholinesterase (AChE) in addiction through measurement of enzyme activity and to find potential association of ACHE gene 3′UTR variants rs17228602 and rs17228616 in heroin, hashish and poly drug addicts. Both SNPs are located within microRNA (miRNA) recognition sites with potential to affect miRNA/transcript interaction. A total of 122 addicts of heroin, hashish and polydrug were recruited from local rehabilitation centers to participate in this study. AChE activity was measured in blood by Ellman’s method. SNP genotyping was performed by restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. The AChE activity was found significantly higher (p ≤ ۰٫۰۰۵) in addicted cohort (mean ± standard error of mean 0.020 ± ۰٫۰۰۱ μmol/L/min; 95% confidence interval (CI) 0.018–۰٫۰۲۲) in comparison to non-addicted healthy subjects (0.011 ± ۰٫۰۰۱ μmol/L/min; 95% confidence interval CI 0.010–۰٫۰۱۳). A statistically significant association of ACHE rs17228602 SNP with addiction vulnerability in dominant (DM: Odd’s ratio OR = ۲٫۰۹۵, ۹۵% CI = ۱٫۱۵۷–۳٫۸۰۷ p = ۰٫۰۰۹) and allelic genetic models (OR = ۱٫۸۵۴ ۹۵% CI = ۱٫۰۸۲–۳٫۱۸۷, p = ۰٫۰۱۶) was observed. However, no statistically significant association of rs17228616 SNP with substance abuse disorder was found. The data presented here shows that AChE could play significant role in substance addiction. Further studies with larger sample size and other variants of AChE are recommended to identify novel therapeutic approaches for cholinergic based treatment of addiction.

Introduction

Drug addiction is a persistent relapsing mental disorder encompassing uncontrollable drug use and severe emotional impairment. Repeated intake of illicit drugs changes several brain regions making drug seeking a compulsive and sole purpose of addict’s life, eventually harming the physiological and physical well-being of the addicted individual [1,2]. There are many substances that can lead to addiction if used excessively including but not limited to heroin, alcohol, cocaine, cannabis, ice and opioids [3]. Worldwide estimates put the number of addicts to an estimated 27.8 million according to United Nations Office of Drugs and Crime (UNODC). In Pakistan, around 6.7 million people have been reported to abuse drugs at least once in their life and, 4.25 million of them became heroin dependent according to 2013 UNODC report. Due to considerable morbidity and mortality, drug addiction is a serious socioeconomic concern besides spreading many infectious diseases like hepatitis B and C, HIV etc. It is also associated with psychiatric disorders like anxiety and depression. Drug addiction is a multifactorial disorder involving genetics, epigenetics, environment, type of illicit drugs, route of drug administration, physiological and socioeconomic factors [4].