title: Association study of the SLC6A3 VNTR (DAT) and DRD2/ANKK1 Taq1A polymorphisms with alcohol dependence in a population from northeastern Brazil.
abstract: BACKGROUND
  Alcohol dependence (AD) is a complex psychiatric disorder, affecting 5.4% of the general population lifetime, characterized by excessive alcohol consumption influenced by environmental risk factors and genetic factors. Genetic alterations in dopaminergic system are involved in the treatment and etiology of AD. The aim of this search was to test the association of the SLC6A3 40 bp-VNTR and DRD2/ANKK1 Taq1A single nucleotide polymorphism (SNP), a transporter and receptor of the dopaminergic system, with AD through a study in a population of northeastern Brazil.
  
  
  METHODS
  The study design was a case-control that included 227 males of northeastern Brazil (113 alcoholics and 114 controls). Alcoholics were classified according to the DSM-IV criteria for AD and controls were subjects who had nonalcohol problems or who never drank. Genotyping was detected through polymerase chain reaction (PCR) for SLC6A3 40 bp-VNTR and RFLP-PCR for DRD2/ANKK1 Taq1A, and subsequent electrophoresis on a 2% agarose gel. The distribution of allele and genotype frequencies and association of polymorphisms with AD were assessed by chi-square, Fisher's exact test, and odds ratio (OR) with a confidence interval of 95% and significance p < 0.05. Data were analyzed on BioEstat 5.3 software.
  
  
  RESULTS
  The SLC6A3 40 bp-VNTR was associated with AD, allelic, and genotypic frequencies were significantly different, respectively (A9 vs. A10: OR = 1.88; p = 0.01; A9/A9 vs. A10/A10: OR = 6.25; p = 0.02; A9/A9 vs. A9/A10 + A10A10: OR = 5.44; p = 0.03). However, there was no statistically significant difference when the allelic (p = 0.10) and genotypic (p > 0.05) frequencies for DRD2/ANKK1 Taq1A were compared.
  
  
  CONCLUSIONS
  These findings suggest that A9 allele and A9/A9 genotype of the SLC6A3 40 bp-VNTR are involved in the vulnerability to AD in the population studied. However, for the DRD2/ANKK1 SNP does not present contributions to the development of AD.
authors: Genetics and Molecular Biology Laboratory, Federal University of Piauí, Parnaíba, Brazil.
authors: Any Carolina C G
authors: AC
authors: Vasconcelos
authors: Edmilson de Souza R
authors: Ede S
authors: Neto
authors: Giovanny R
authors: GR
authors: Pinto
authors: France Keiko N
authors: FK
authors: Yoshioka
authors: Fábio José N
authors: FJ
authors: Motta
authors: Daniel Fernando P
authors: DF
authors: Vasconcelos
authors: Renata
authors: R
authors: Canalle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000235:genetics*; D001938:Brazil; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Alcoholism; Brain Reward System; Dopamine Transporter Gene; Genetic Epidemiology