Association of paraoxonase (PON)1 activity, glutathione S-transferase GST T1/M1 and STin.2 polymorphisms with comorbidity of tobacco use disorder and mood disorders

•We examine the biological underpinnings of comorbid mood and tobacco use disorder (TUD).•Comorbid TUD and mood disorders are associated with lower paraoxonase 1 activity.•This comorbidity is associated with the STin2.10/10 genotype and STin2.12 allele.•This comorbidity is associated with the glutathione-S-transferase T1/M1 null genotype.•The comorbidity is associated with oxidative and serotonin signaling pathways. There is evidence that genetic factors influence the probability of comorbidity of tobacco use disorder (TUD) with mood disorders. This study was carried out to examine whether both TUD and mood disorders are associated with genetic biomarkers particularly paraoxonase 1 (PON1) status, polymorphisms of glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the STIn 2 polymorphism of the serotonin transporter. PON1 status (Q192R polymorphism and PON1 plasmatic activity), GSTM1, GSTT1, and STin.2 genotypes and alleles were assayed in 4 mutually exclusive study groups, i.e., comorbid mood disorder and TUD (n=95); TUD without mood disorders (n=90); mood disorders but no TUD (n=62); and controls (never-smokers without mood disorders; n=113). Logistic regression analyses showed that comorbid mood disorders and TUD were associated with significantly lower PON1 activity, the STin2.10/10 genotype (protective) or the Stin2.12 allele (risk factor) and the GSTM1 and GSTT1 null genotypes (protective). These results show that comorbid mood disorders and TUD are associated with specific biomarkers related to oxidative stress and serotonin pathways.