Association of status of acetylcholinesterase and ACHE gene 3’ UTR variants (rs17228602, rs17228616) with drug addiction vulnerability in pakistani population

Javed, Tahira; Habib, Rabia; Ghafoor, Sania; Rumman, Baseerat; Awan, Sliha; Ntepe, Leonel J.M.; Batool, Sajida; Nurulain, Syed M.

doi:10.1016/j.cbi.2019.05.036

Cited by 9 publications

(6 citation statements)

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“…For instance, Abdel-Salam and Khadrawy [18] reported a decrease in serum AChE activity in rats when subcutaneously treated with cannabis resin. Sadaf et al and Javed et al [25,45] reported elevated AChE activity in hashish users. Luthra et al [46] found that prolong treatment (180 days) in rats caused slight elevation of AChE compared to moderate inhibition by treatment up to 90 days in the brain of male rats.…”

Section: Discussionmentioning

confidence: 96%

“…It has been previously reported that polymorphisms in cannabinoid receptor 1 gene, referred to as cannabinoid receptor 1 (CNR1), are associated with tendency to substance abuse [21] and diseases like Alzheimer [22], psychotic disorders [23], alcohol dependence [22], and nicotine dependence [24]. Similarly, ACHE rs17228602 has been found to be associated with drug abuse vulnerability [25]. The aim of the present study was to investigate the interactions of some of the constituents of cannabis with AChE by molecular docking, in silico logP determination and measure the AChE in the blood of cannabis addicted individuals compared to healthy controls.…”

Section: Introductionmentioning

confidence: 99%

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Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602

et al. 2020

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The study documented here was aimed to find the molecular interactions of some of the cannabinoid constituents of cannabis with acetylcholinesterase (AChE). Molecular docking and LogP determination were performed to predict the AChE inhibitory effect and lipophilicity. AChE enzyme activity was measured in the blood of cannabis addicted human subjects. Further, genetic predisposition to cannabis addiction was investigated by association analysis of cannabinoid receptor 1 (CNR1) single nucleotide polymorphism (SNP) rs806368 and ACHE rs17228602 using restriction fragment length polymorphism (RFLP) method. All the understudied cannabis constituents showed promising binding affinities with AChE and are lipophilic in nature. The AChE activity was observed to be indifferent in cannabis addicted and non-addicted healthy controls. There was no significant association with CNR1 SNP rs806368 and ACHE rs17228602. The study concludes that in silico prediction for individual biomolecules of cannabis is different from in vivo physiological action in human subjects when all are present together. However, for a deeper mechanistic insight into these interactions and association, multi-population studies are suggested. Further studies to explore the inhibitory potential of different cannabis constituents for intended AChE inhibitor-based drug are warranted.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602

et al. 2020

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“…The activity of AChE turned out to be decreased in samples with atypical seminal parameters like sperm concentration and motility [46]. According to the literature, acetylcholinesterase read-through variant (AChE-R) activity is overexpressed in stress-induced male infertility [30] whereas AChE-R is depicted to govern by miR125b, one of the micro-RNAs regulated by ACHE SNPs present in 3 UTR region [28]. Based on this fact, it may be assumed that the faulty communication of miR-125b/ACHE variant rs17228602 adversely affects the relevant regulation of cholinergic signalling and pathways, leading to pathophysiological conditions like reproductive infertility.…”

Section: Plos Onementioning

confidence: 99%

“…The ACHE gene is considered conserved amongst populations. Exome Aggregation Consortium reported approximately 141 synonymous mutations and 137 missense variants for the ACHE gene [28]. ACHE encoding gene spans about 6kb and is located at chromosomal position 7q22.…”

Section: Introductionmentioning

confidence: 99%

Acetylcholinesterase, pro-inflammatory cytokines, and association of ACHE SNP rs 17228602 with male infertility

et al. 2023

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Male infertility is a complex and polygenic reproductive disease. 10–15% of the males are affected by idiopathic infertility conditions. Acetylcholine (ACh), a major neurotransmitter has been reported to play a non-neuronal role as well. Acetylcholinesterase (AChE) is the primary ACh hydrolyzing enzyme whose over or lower expression influence the availability of ACh for physiological roles. The purpose of the study was to find the possible impact and association of acetylcholinesterase, ACHE gene variant rs 17228602, and pro-inflammatory cytokines in clinically diagnosed infertile males. The study includes clinically diagnosed fifty non-infertile (control) and forty-five infertile males. Whole blood AChE enzymatic activity was measured. Genotyping of rs17228602 was carried out from peripheral blood by standard molecular methods. Pro-inflammatory cytokines were determined by the ELISA method. AChE enzyme was found to be significantly elevated in infertile than non-infertile males. ACHE SNP rs17228602 had shown significant association in dominant model (odd ratio = 0.378, 95% CI = 0.157–0.911, p-value 0.046). Pro-inflammatory cytokine IL-1β was notably increased with statistical significance (p ≤0.05) in male infertile patients. The study concludes and speculates that AChE plays role in the pathogenesis of male infertility through the modulation of inflammatory pathways. Further studies in this direction may resolve the idiopathic cases of male infertility. Other variants of ACHE and the association of miRNA for the regulation of AChE in male infertility are suggested for further insight.

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“…More importantly, fathers suffering from SUDs had a great impact on the mental health of their offspring [3]. In addition, the heritability was reported as 54% among drug addicts according to polygenic scores(PGSs) [4,5]. Therefore, the individual identi cation and gene polymorphism of SUDs has been the key points in recent years' studies.…”

Section: Introductionmentioning

confidence: 99%

The Allele Frequency Variation of Autosomal 19 Short Tandem Repeat (STR) Loci in Drug Abuser: A Pilot Study

Lin¹,

Zhang²,

Su³

et al. 2020

Preprint

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Backgrounds: Substance use disorders (SUDs) refers to drug abuse of 10 separate classes impacting seriously mental health.Objective: This study aims to explore the genetic polymorphism of the 19 short tandem repeat (STR) loci (D19S433, D5S818, D21S11, D18S51, D6S1043, D3S1358, D13S317, D7S820, D16S539, CSF1PO, Penta D, VWA, D8S1179, TPOX, Penta E, TH01, D12S391, D2S1338, and FGA) and the risk genetic factors of substance use disorders(SUDs).Methods: The capillary electrophoresis was applied to analyze 19 STR loci in 156 drug abusers. The data of 6,134 healthy people in a previous study were applied to contrast as the control group. The differences in the frequency of the gene were analyzed by Chi-square test. Results: The gene distributions of 19 STR in drug addicts were consistent with hereditary rules. The frequency of vWA, FGA, Penta E was significantly different between the drug abuser and the control group (P<0.05).Conclusion: The 19 STR loci might provide highly informative polymorphic data for addicted genetic studies. Furthermore, there might be a predisposing gene for the drug abuser.

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Association of status of acetylcholinesterase and ACHE gene 3’ UTR variants (rs17228602, rs17228616) with drug addiction vulnerability in pakistani population

Cited by 9 publications

References 25 publications

Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602

Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602

Acetylcholinesterase, pro-inflammatory cytokines, and association of ACHE SNP rs 17228602 with male infertility

The Allele Frequency Variation of Autosomal 19 Short Tandem Repeat (STR) Loci in Drug Abuser: A Pilot Study

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Association of status of acetylcholinesterase and ACHE gene 3’ UTR variants (rs17228602, rs17228616) with drug addiction vulnerability in pakistani population

Cited by 9 publications

References 25 publications

Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602

Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602

Acetylcholinesterase, pro-inflammatory cytokines, and association of ACHE SNP rs 17228602 with male infertility

The Allele Frequency Variation of Autosomal 19 Short Tandem Repeat (STR) Loci in Drug Abuser:&nbsp;A Pilot Study

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The Allele Frequency Variation of Autosomal 19 Short Tandem Repeat (STR) Loci in Drug Abuser: A Pilot Study