Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.

<h4>Objective</h4>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. Butyry...

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Autores principales:	André Brooking Negrão, Alexandre Costa Pereira, Camila Guindalini, Hadassa Campos Santos, Guilherme Peres Messas, Ronaldo Laranjeira, Homero Vallada
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b8137151901549729f56fdf68e98ae62
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spelling	oai:doaj.org-article:b8137151901549729f56fdf68e98ae622021-11-18T08:44:26ZButyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.1932-620310.1371/journal.pone.0080505https://doaj.org/article/b8137151901549729f56fdf68e98ae622013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24312228/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.André Brooking NegrãoAlexandre Costa PereiraCamila GuindaliniHadassa Campos SantosGuilherme Peres MessasRonaldo LaranjeiraHomero ValladaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80505 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q André Brooking Negrão Alexandre Costa Pereira Camila Guindalini Hadassa Campos Santos Guilherme Peres Messas Ronaldo Laranjeira Homero Vallada Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
description	<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
format	article
author	André Brooking Negrão Alexandre Costa Pereira Camila Guindalini Hadassa Campos Santos Guilherme Peres Messas Ronaldo Laranjeira Homero Vallada
author_facet	André Brooking Negrão Alexandre Costa Pereira Camila Guindalini Hadassa Campos Santos Guilherme Peres Messas Ronaldo Laranjeira Homero Vallada
author_sort	André Brooking Negrão
title	Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
title_short	Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
title_full	Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
title_fullStr	Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
title_full_unstemmed	Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
title_sort	butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b8137151901549729f56fdf68e98ae62
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Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.

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