Association of the Uncoupling Protein 2-866 G/A Polymorphism with Family History and Duration of Tobacco Use Disorder in a Turkish Population.

Background: A variety of substances cause neurotoxicity by increasing intracellular oxidative stress, followed by mitochondrial dysfunction. Uncoupling proteins (UCPs) act as membrane transport proteins and reduce reactive oxygen products and mitochondrial calcium influx. We aimed to study UCP2-866 G/A gene polymorphism in tobacco use disorder (TUD) by comparing genotype distributions between TUD patients and healthy controls considering clinical parameters. Methods: One hundred eighteen patients with TUD and 96 healthy volunteers were included in the study. The diagnosis of the patients were then confirmed, based on the DSM-5 criteria. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to determine UCP2 gene polymorphism. Results: Our results demonstrated that the UCP2 genotype distribution and allele frequencies of the TUD patient group were significantly different from those of the control group. When the UCP2 genotype and the allele frequency distributions were compared between the two groups according to the family history of TUD in the patient group, the UCP2 genotype and allele frequency distributions were significantly different. The GG genotype or G allele percentage was significantly higher in patients with a family history of TUD, than the patients without a family history of TUD. Comparing clinical parameters based on the UCP2 genotype, the disorder's duration was significantly different between the groups of UCP2 genotype. The duration of TUD was significantly shorter in patients with GG genotype than other genotypes. Conclusions: In summary, the UCP2-866 G/A gene polymorphism might be associated with family history and duration of TUD in Turkish patients.

Evaluation of COMT (rs4680), CNR2 (rs2501432), CNR2 (rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants in synthetic cannabinoid use disorder patients.

Synthetic cannabinoids (SC) are psychoactive drugs that generally produce more severe clinical outcomes compared to Δ9-tetrahydrocannabinol. This study aimed to evaluate the relationship between clinical features of synthetic cannabinoid use disorder (SCUD) and COMT (rs4680), CNR2 (rs2501432), CNR2 (rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants in SCUD patients by comparing the genotype distributions of gene variants between patients and healthy controls. Based on the DSM-5 criteria, 94 patients with SCUD, confirmed with a positive urine test, and 95 healthy volunteers were included in the study. Self-mutilation, suicidal behavior, psychotic symptoms, drug-induced psychosis, tobacco use disorder (TUD) or alcohol use disorder (AUD) comorbidity, and family history of TUD or AUD were evaluated in all patients. PCR-RFLP was used to identify gene variants from DNA material. The distributions of CNR2 (rs2229579) and UCP2 (rs659366) variants were significantly different in patients diagnosed with SCUD compared to the control group. SC-related psychotic symptoms were associated with the IL-17 (rs763780) variant in SCUD patients who had an onset of SC usage under 18 years of age. While the COMT Val108Met gene variant was related to self-mutilation, the COMT Val158Met variant was associated with attempted suicide. In addition, in SCUD patients, the UCP2 (rs659366) variant was associated with a family history of AUD or TUD. In summary, CNR2 (rs2229579) and UCP2 (rs659366) variants were associated with SCUD. While SC-related psychotic symptoms were related to the IL-17 (rs763780) variant, the COMT variants were associated with self-mutilation or attempted suicide in SCUD patients.

XRCC4 rs6869366 polymorphism is associated with susceptibility to both nicotine dependence and/or schizophrenia

Abstract Background: Oxidative stress induced DNA damage has been assumed to contribute to the etiopathogenesis of schizophrenia (Sch). Smoking prevalence was more common in patients with Sch. The X-ray repair cross-complementation group 4 (XRCC4) gene plays an important role in the repair of DNA double-strand breaks. Objective: The purpose of this study was to investigate whether XRCC4 rs6869366 polymorphism has a relationship both in nicotine dependence (ND) and Sch+ND risk. Methods: One hundred and four patients with Sch+ND, 133 subjects with ND only and 70 healthy controls were enrolled in the study. XRCC4 rs6869366 polymorphism was analyzed using PCR-RFLP assay. Results: The frequency of XRCC4 rs6869366 GG genotype was more common in the ND and Sch+ND group than controls (p = 0.001 and p = 0.001, respectively). XRCC4 rs6869366 TT genotype was lower in both ND and Sch+ND group compared to controls (p = 0.001 and p = 0.001, respectively). Also, XRCC4 rs6869366 G allele was higher in Sch+ND group than controls (p = 0.001) while XRCC4 rs6869366 T allele was lower in ND group than healthy controls (p=0.001). XRCC4 rs6869366 GT genotype was lower in ND group than control group (p = 0.003). Discussion: These results suggested that the XRCC4 rs6869366 polymorphism G related genotype/allele was associated with susceptibility to both ND and Sch+ND in a Turkish population.