Elsevier

Journal of Affective Disorders

Volume 172, 1 February 2015, Pages 347-354
Journal of Affective Disorders

Research Report
STin2 VNTR polymorphism is associated with comorbid tobacco use and mood disorders

https://doi.org/10.1016/j.jad.2014.10.023Get rights and content

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.

Aims

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.

Section snippets

Background

Many studies have reported on the comorbidity between mood disorders and tobacco use disorder (TUD) (Patton et al., 1998, Lasser et al., 2000, Glassman et al., 2001, Murphy et al., 2003, Klungsøyr et al., 2006, Ziedonis et al., 2008, Pasco et al., 2008, Berlin et al., 2009, Pedersen and von Soest, 2009, Boden et al., 2010, Flensborg-Madsen et al., 2011, Jamal et al., 2012, Goodwin et al., 2013). Estimates of the prevalence rate of current TUD among individuals with major depressive disorder and

Study population

In this cross-sectional, case-control study, we included participants recruited from the outpatient Centre of Approach and Treatment for Smokers and from staff at Londrina State University (UEL), Paraná, Brazil. This is a re-analysis of previously published data presenting the STin2 VNTR polymorphism in TUD in relation to nicotine dependence characteristics (Pizzo de Castro et al., 2014). The actual study re-analyzes the data with respect to the comorbidity TUD and mood disorders. All

Socio-demographic and clinical characteristics

Table 1 shows the socio-demographic and clinical characteristics of the 4 study groups, i.e. 1) never-smokers without mood disorders (the controls); 2) never-smokers with mood disorders; 3) TUD subjects without mood disorder; 4) patients with comorbid mood disorders and TUD. Without p-correction, there were marginal but significant differences in age between the groups: group 3 patients were older than controls (Tukey test: p=0.003). There were significantly more females in the mood disorder

Discussion

The current study demonstrates that patients with TUD and comorbid depression or bipolar disorder show a significant increased frequency of the STin.12 allele and a lowered frequency of the STin2.10/10 genotype. These findings suggest that the STin2.12 allele increases risk to TUD with either depression or bipolar disorder, whereas the STin2.10/10 genotype shows a protective effect. Contrary to expectation, there were no significant changes in the frequencies of the STin2 alleles and genotypes

Role of funding source

This study was supported by Health Sciences Postgraduate Program at Londrina State University, Paraná, Brazil (UEL) and Fundação Araucária. MB is supported by a NHMRC Senior Principal Research Fellowship 1059660. MM is supported by a CNPq (Conselho Nacional de Desenvolvimento Cientifico e Technologia) (Grant no. 404877/2013-3) PVE fellowship at the Health Sciences Graduate Program, Londrina State University, Londrina, Paraná, Brazil (UEL) (Grant no. 40002012046P0).

Conflict of interest

The authors declare that they have no competing interests.

Acknowledgments

The authors wish to thank the Centre of Approach and Treatment for Smokers, Molecular Genetics Laboratory, and Clinical Immunology section of Clinical Analysis Laboratory of University Hospital of Londrina State University, Paraná, Brazil (UEL).

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