Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
paper
Cited
Public
- Authors
- Negrão, André Brooking; Pereira, Alexandre Costa; Guindalini, Camila; Santos, Hadassa Campos; Messas, Guilherme Peres; Laranjeira, Ronaldo; Vallada, Homero
- Year
- 2013
- Journal
- PloS one
- PMID
- 24312228
- DOI
- 10.1371/journal.pone.0080505
- PMCID
- PMC3842332
OBJECTIVE: The search for genetic vulnerability factors in cocaine dependence has focused on the role that neuroplasticity plays in addiction. However, like many other drugs, the ability of an individual to metabolize cocaine can also influence susceptibility to dependence. Butyrylcholinesterase (BChE) metabolizes cocaine, and genetic variants of the BChE gene (BCHE) alter its catalytic activity. Therefore, we hypothesize that cocaine users with polymorphisms in BCHE can show diverse addictive behaviors due to differences in effective plasma concentrations of cocaine. Those polymorphisms might also influence users to prefer one of the two main preparations (crack or powder cocaine), despite having equal access to both. The present work investigates polymorphisms in BCHE and if those genetic variants constitute risk factors for cocaine dependence and for crack cocaine use. METHODS: A total of 1,436 individuals (698 cocaine-dependent patients and 738 controls) were genotyped for three single nucleotide polymorphisms (SNPs) in BCHE: rs1803274, rs4263329, and rs4680662. RESULTS: For rs4263329, a nominal difference was found between cases and controls. For rs1803274 (the functional SNP), a statistically significant difference was found between patients who used crack cocaine exclusively and those who used only powder cocaine (P = 0.027; OR = 4.36; 95% CI = 1.18-16.04). Allele frequencies and genotypes related to other markers did not differ between cases and controls or between the two cocaine subgroups. CONCLUSIONS: Our findings suggest that the AA genotype of rs1803274 is a risk factor for crack cocaine use, which is more addictive than powder cocaine use. Further studies are needed in order to confirm this preliminary result and clarify the role of BCHE and its variants in cocaine dependence.
Population Structure Analysis.Graphic representation of the first two principal components for cases and controls genotyped with 64 AIMs, each point in this plot is an individual. The distribution of individuals in the axes is similar for both groups therefore the EIGENSTRAT software was not able to detect a difference in population stratification between cases and controls.
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry. | 2017 | 28070124 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Association of BCHE gene SNP rs1803274 (K-variant) and rs3495 with obesity in Pakistani population group. | Amir A et al. | — | 2025 | → |
| Black and non-black population: investigation of the difference in butyrylcholinesterase activity in a healthy population in Salvador, Bahia. | da Conceição Filho JN et al. | — | 2023 | → |
| Long-Chain Acylcholines Link Butyrylcholinesterase to Regulation of Non-neuronal Cholinergic Signaling. | Kinchen JM et al. | — | 2022 | → |
| Biochemical Analysis and Association of Butyrylcholinesterase SNPs rs3495 and rs1803274 with Substance Abuse Disorder. | Munir S et al. | — | 2019 | → |
| Wastewater-based epidemiology in low Human Development Index states: bias in consumption monitoring of illicit drugs. | Devault DA et al. | — | 2018 | → |
| An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry. | Meyers JL et al. | — | 2017 | → |