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Genetic polymorphisms in glutathione-S-transferases are associated with anxiety and mood disorders in nicotine dependence

Odebrecht Vargas Nunes, Sandraa,b; Pizzo de Castro, Márcia Reginaa; Ehara Watanabe, Maria Angelicac; Losi Guembarovski, Robertac; Odebrecht Vargas, Hebera,b; Vissoci Reiche, Edna Mariad; Kaminami Morimoto, Helenad; Dodd, Seetale,f,g; Berk, Michaele,f,g

doi: 10.1097/YPG.0000000000000023
Original Articles

Background Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence.

Materials and methods Smokers were recruited at the Centre of Treatment for Smokers. The instruments were a sociodemographic questionnaire, Fagerström Test for Nicotine Dependence, diagnoses of mood disorder and nicotine dependence according to DSM-IV (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Anxiety disorder was assessed based on the treatment report. Laboratory assessment included glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), which were detected by a multiplex-PCR protocol.

Results Compared with individuals who had both GSTM1 and GSTT1 genes, a higher frequency of at least one deletion of the GSTM1 and GSTT1 genes was identified in anxious smokers [odds ratio (OR)=2.21, 95% confidence interval (CI)=1.05–4.65, P=0.034], but there was no association with bipolar and unipolar depression (P=0.943). Compared with nonanxious smokers, anxious smokers had a greater risk for mood disorders (OR=4.67; 95% CI=2.24–9.92, P<0.001), lung disease (OR=6.78, 95% CI=1.95–23.58, P<0.003), and suicide attempts (OR=17.01, 95% CI=2.23–129.91, P<0.006).

Conclusion This study suggests that at least one deletion of the GSTM1 and GSTT1 genes represents a risk factor for anxious smokers. These two genes may modify the capacity for the detoxification potential against oxidative stress.

aCenter of Approach and Treatment for Smokers, University Hospital, Londrina State University

bDepartment of Psychiatry, Health Sciences Center

cDepartment of Pathological Sciences, Biological Sciences Center

dDepartment of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, Londrina State University, Londrina, Paraná, Brazil

eIMPACT Strategic Research Centre, School of Medicine, Deakin University

fBarwon Health and the Geelong Clinic, Swanston Centre, Geelong, Victoria

gDepartment of Psychiatry, Orygen Youth Health Research Centre, Centre for Youth Mental Health, The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia

Correspondence to Sandra Odebrecht Vargas Nunes, MD, PhD, Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, Campus Universitário/Cx, Postal 6001/Zip 86051-990, Londrina, Paraná, Brazil Tel: +55 43 33391178; fax: +55 43 33238210; e-mail:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Received March 3, 2013

Accepted October 25, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins