title: Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes.
abstract: 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.
authors: Department and Institute of Psychiatry (LIM 23), University of São Paulo Medical School, São Paulo, SP, Brazil ; Laboratory of Genetics and Molecular Cardiology (LIM 13), Heart Institute-InCor, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors: André Brooking
authors: AB
authors: Negrão
authors: Alexandre Costa
authors: AC
authors: Pereira
authors: Camila
authors: C
authors: Guindalini
authors: Hadassa Campos
authors: HC
authors: Santos
authors: Guilherme Peres
authors: GP
authors: Messas
authors: Ronaldo
authors: R
authors: Laranjeira
authors: Homero
authors: H
authors: Vallada
mesh_terms: D000328:Adult; D000483:Alleles; D002091:Butyrylcholinesterase / Q000235:genetics*; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
chemical_list: D002091:Butyrylcholinesterase