Butyrylcholinesterase Genetic Variants: Association with Cocaine Dependence and Related Phenotypes

André Brooking Negrão,Alexandre Costa Pereira,Hadassa Campos Santos,Ronaldo Laranjeira,Camila Guindalini,Guilherme Peres Messas,Homero Vallada

doi:10.1371/journal.pone.0080505

André Brooking Negrão, Alexandre Costa Pereira + Show 5 more

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https://doi.org/10.1371/journal.pone.0080505

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Abstract

ObjectiveThe 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.MethodsA 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.ResultsFor 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.ConclusionsOur 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.

Highlights

Cocaine addiction is a complex behaviour that arises from the interactions between genetic and environmental risk factors
For rs1803274, a statistically significant difference was found between patients who used crack cocaine exclusively and those who used only powder cocaine (P = 0.027; odds ratio (OR) = 4.36; 95% CI = 1.18–16.04)
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

Summary

Introduction

Cocaine addiction is a complex behaviour that arises from the interactions between genetic and environmental risk factors. Some studies have already reported genetic markers in dopaminergic brain systems associated with cocaine dependence [3,4,5]. Many of those markers are associated with other psychiatric disorders or substancerelated disorders other than cocaine-related disorders and might not be specific markers for the cocaine dependency risk [6,7,8]. The results of twin studies indicate that the heritability of substance dependence can be general or drugspecific, suggesting that specific genetic markers increase susceptibility to dependence on distinct drugs [9,10]. In one of the largest studies of cocaine dependence to date [3] various polymorphisms were found to be associated with the cocaine-dependent phenotype, as has been demonstrated in animal studies involving markers related to the dopaminergic reward system and to other biochemical pathways [11,12]

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