title: A 40-bp VNTR polymorphism in the 3'-untranslated region of DAT1/SLC6A3 is associated with ADHD but not with alcoholism.
abstract: BACKGROUND
  ADHD and alcoholism are psychiatric diseases with pathophysiology related to dopamine system. DAT1 belongs to the SLC6 family of transporters and is involved in the regulation of extracellular dopamine levels. A 40 bp variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1/SLC6A3 gene was previously reported to be associated with various phenotypes involving disturbed regulation of dopaminergic neurotransmission.
  
  
  METHODS
  A total of 1312 subjects were included and genotyped for 40 bp VNTR polymorphism of DAT1/SLC6A3 gene in this study (441 alcoholics, 400 non-alcoholic controls, 218 ADHD children and 253 non ADHD children). Using miRBase software, we have performed a computer analysis of VNTR part of DAT1 gene for presence of miRNA binding sites.
  
  
  RESULTS
  We have found significant relationships between ADHD and the 40 bp VNTR polymorphisms of DAT1/SLC6A3 gene (P < 0.01). The 9/9 genotype appeared to reduce the risk of ADHD about 0.4-fold (p < 0.04). We also noted an occurrence of rare genotypes in ADHD (frequency different from controls at p < 0.01). No association between alcoholism and genotype frequencies of 40 bp VNTR polymorphism of DAT1/SLC6A3 gene has been detected.
  
  
  CONCLUSIONS
  We have found an association between 40 bp VNTR polymorphism of DAT1/SLC6A3 gene and ADHD in the Czech population; in a broad agreement with studies in other population samples. Furthermore, we detected rare genotypes 8/10, 7/10 and 10/11 present in ADHD boys only and identified miRNAs that should be looked at as potential novel targets in the research on ADHD.
authors.affiliation: Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic. omarsery@sci.muni.cz.|Institute of Animal Physiology and Genetics, Academy of Science, Veveří 97, 602 00, Brno, Czech Republic. omarsery@sci.muni.cz.
authors.forename: Omar
authors.initials: O
authors.lastname: Šerý
authors.affiliation: Department of Psychiatry, 1st Faculty of Medicine, Charles University, Ke Karlovu 11, 121 08, Prague, Czech Republic. ivopaclt@seznam.cz.
authors.forename: Ivo
authors.initials: I
authors.lastname: Paclt
authors.affiliation: Department of Psychiatry, Masaryk University, Faculty of Medicine, Kamenice 5, 625 00, Brno, Czech Republic. idrtilkova@fnbrno.cz.
authors.forename: Ivana
authors.initials: I
authors.lastname: Drtílková
authors.affiliation: Department of Psychiatry, Masaryk University, Faculty of Medicine, Kamenice 5, 625 00, Brno, Czech Republic. ptheiner@fnbrno.cz.
authors.forename: Pavel
authors.initials: P
authors.lastname: Theiner
authors.affiliation: Department of Psychiatry, 1st Faculty of Medicine, Charles University, Ke Karlovu 11, 121 08, Prague, Czech Republic. Marta.Kopeckova@seznam.cz.
authors.forename: Marta
authors.initials: M
authors.lastname: Kopečková
authors.affiliation: Department of Psychiatry, 1st Faculty of Medicine, Charles University, Ke Karlovu 11, 121 08, Prague, Czech Republic. p.zvolsky@seznam.cz.
authors.forename: Petr
authors.initials: P
authors.lastname: Zvolský
authors.affiliation: Laboratory of Neurochemistry, School of Medical Sciences (Discipline of Anatomy and Histology) and Bosch Institute, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. vibar@anatomy.usyd.edu.au.
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Balcar
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000453:epidemiology* / Q000235:genetics*; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D003198:Computer Simulation; D018153:Czech Republic / Q000453:epidemiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D009483:Neuropsychological Tests
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human