title: STin2 VNTR polymorphism is associated with comorbid tobacco use and mood disorders.
abstract: BACKGROUND
  There is a significant comorbidity between mood disorders and tobacco use disorder (TUD), which may be related to both genetic and environmental factors. Gene variants of the 5-HT transporter, such as STin2 VNTR (a variable number of tandem repeats in the functional serotonin transporter intron 2) may be associated with mood disorders and TUD.
  
  
  OBJECTIVE
  This study aimed to delineate the association between the STin2 genetic polymorphism and comorbid TUD and mood disorders, including depression or bipolar disorder.
  
  
  METHODS
  We examined the STin2 VNTR polymorphism in never-smokers (n=113); patients with mood disorders without TUD (n=62); patients with TUD without mood disorders (n=90); and patients with both disorders (n=95).
  
  
  RESULTS
  We found a significant association between the STin2 genetic polymorphism and the above diagnostic groups whereby the STin2.12 allele shows a positive association with comorbid TUD and mood disorders (Odds ratio=3.07, 95% CI=1.41-6.68), while the STin2.10/10 homozygous genotype shows a negative association (Odds ratio=0.34, 95% CI=0.16-0.74). Adjusting for years of education, age, gender, marital status and ethnicity did not change these results, but showed that TUD was associated with lower education levels and less stable relationships, whereas mood disorders were related to female gender. A family history of TUD was significantly associated with TUD in subjects without mood disorders only.
  
  
  CONCLUSIONS
  The STin2.12 allele is positively and the STin2.10/10 genotype is negatively associated with comorbid TUD and mood disorders, depression or bipolar depression, suggesting that biological endophenotypes, e.g. disorders in serotonin metabolism, may in part underpin this comorbidity.
authors.affiliation: Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, Campus Universitário, Londrina, Paraná, Brazil. Electronic address: mpizzo@sercomtel.com.br.
authors.forename: Márcia Regina
authors.initials: MR
authors.lastname: Pizzo de Castro
authors.affiliation: Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, Campus Universitário, Londrina, Paraná, Brazil; Department of Clinical Medicine, Health Sciences Center, Londrina State University, University Hospital, Londrina, Paraná, Brazil.
authors.forename: Sandra Odebrecht
authors.initials: SO
authors.lastname: Vargas Nunes
authors.affiliation: Department of Pathological Sciences, Biological Sciences Centre, Londrina State University, Paraná, Brazil.
authors.forename: Roberta Losi
authors.initials: RL
authors.lastname: Guembarovski
authors.affiliation: Department of Pathological Sciences, Biological Sciences Centre, Londrina State University, Paraná, Brazil.
authors.forename: Carolina Batista
authors.initials: CB
authors.lastname: Ariza
authors.affiliation: Department of Pathological Sciences, Biological Sciences Centre, Londrina State University, Paraná, Brazil.
authors.forename: Julie Massayo Maeda
authors.initials: JM
authors.lastname: Oda
authors.affiliation: Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, Campus Universitário, Londrina, Paraná, Brazil; Department of Clinical Medicine, Health Sciences Center, Londrina State University, University Hospital, Londrina, Paraná, Brazil.
authors.forename: Heber Odebrecht
authors.initials: HO
authors.lastname: Vargas
authors.affiliation: Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, Campus Universitário, Londrina, Paraná, Brazil.
authors.forename: Luiz Gustavo
authors.initials: LG
authors.lastname: Piccoli de Melo
authors.affiliation: Department of Pathological Sciences, Biological Sciences Centre, Londrina State University, Paraná, Brazil.
authors.forename: Maria Angelica Ehara
authors.initials: MA
authors.lastname: Watanabe
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia; Orygen Youth Health Research Centre, Centre for Youth Mental Health, Department of Psychiatry and the Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; Barwon Health and the Geelong Clinic, Swanston Centre, Geelong, Victoria, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia; Department of Psychiatry, Chulalongkorn University, Faculty of Medicine, Bangkok, Thailand; Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Brazil. Electronic address: dr.michaelmaes@hotmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics; D015897:Comorbidity; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D019964:Mood Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: Genetic polymorphism; Inflammation; Mood disorders; Oxidative stress; Serotonin transporter; Tobacco use disorder