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Open Access Highly Accessed Research article

SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study

Márcia Regina Pizzo de Castro1, Michael Maes234*, Roberta Losi Guembarovski5, Carolina Batista Ariza5, Edna Maria Vissoci Reiche6, Heber Odebrecht Vargas1, Mateus Medonça Vargas1, Luiz Gustavo Piccoli de Melo1, Seetal Dodd278, Michael Berk278, Maria Angelica Ehara Watanabe5 and Sandra Odebrecht Vargas Nunes1

Author Affiliations

1 Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, Campus Universitário/Cx, Postal 600, Londrina, Paraná ZIP 86051-990, Brazil

2 IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia

3 Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

4 Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil

5 Department of Pathological Sciences, Biological Sciences Centre, Londrina State University, Londrina, Paraná, Brazil

6 Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Canter, Londrina State University, Londrina, Paraná, Brazil

7 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

8 Barwon Health and the Geelong Clinic, Swanston Centre, Geelong, Victoria 3220, Australia

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BMC Genetics 2014, 15:78  doi:10.1186/1471-2156-15-78

Published: 27 June 2014



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.


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.


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.

STin2 VNTR; Tobacco use disorder; Smoking cessation; Serotonin; Inflammation; Oxidative stress; Polymorphism; Genetic