title: SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study.
abstract: BACKGROUND
  The aim of this study was to determine if variable number of tandem repeats (VNTR) in the second intron (STin2) of the serotonin transporter (SLC6A4) gene was associated with tobacco use disorder, successful smoking cessation, or smoking characteristics. In this case-control study, patients with current tobacco use disorder, diagnosed according to DSM IV criteria (n = 185), and never-smokers, diagnosed according to CDC criteria (n = 175), were recruited and received 52 weeks of combined pharmacotherapy and cognitive therapy. Successful smoking cessation was defined as exhaled carbon monoxide < 6 ppm. SLC6A4 gene STin2 VNTR polymorphism was assessed using a Multiplex-PCR-based method. At baseline, participants were evaluated using the Fagerström Test for Nicotine Dependence (FTND) and the ASSIST scale.
  
  
  RESULTS
  The STin2.12 allele (OR = 2.45; 95% CI = 1.44-4.15, p < 0.001) was associated with an increased risk for tobacco use disorder, while the STin2.10/10 genotype (OR = 0.42; 95% CI 0.25-0.71, p < 0.001) decreased risk. There were no significant associations between tobacco use disorder and the STin2.10 or STin2.9 alleles or the other genotypes (STin2.12/12, 12/10, 12/9, 10/9 or 9/9). There were no significant associations between the STin2 genotypes and alleles and successful smoking cessation, smoking characteristics and increased alcohol or sedative use risk.
  
  
  CONCLUSIONS
  Our results suggest that the STin2.10/10 genotype and STin2.12 allele are associated with tobacco use disorder or nicotine dependence, but not with treatment response or severity of dependence. It is hypothesized that the ST2in.12 allele by modulating the metabolism of serotonin may participate in the pathophysiology of tobacco use disorder or nicotine dependence.
authors: Márcia Regina
authors: MR
authors: Pizzo de Castro
authors: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia. dr.michaelmaes@hotmail.com.
authors: Michael
authors: M
authors: Maes
authors: Roberta Losi
authors: RL
authors: Guembarovski
authors: Carolina Batista
authors: CB
authors: Ariza
authors: Edna Maria Vissoci
authors: EM
authors: Reiche
authors: Heber Odebrecht
authors: HO
authors: Vargas
authors: Mateus Medonça
authors: MM
authors: Vargas
authors: Luiz Gustavo Piccoli
authors: LG
authors: de Melo
authors: Seetal
authors: S
authors: Dodd
authors: Michael
authors: M
authors: Berk
authors: Maria Angelica Ehara
authors: MA
authors: Watanabe
authors: Sandra Odebrecht Vargas
authors: SO
authors: Nunes
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D016540:Smoking Cessation; D014029:Tobacco Use Disorder / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins