Browsing by Author "Savic-Radojevic, Ana R. (16246037100)"

Objective: To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age. Methods: We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and Schizophrenia-Life-Time Version (K-SADS-PL) interviews. Results: Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype. Conclusion: The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders. © 2016 American Society for Clinical Pathology, 2016. All rights reserved.

Purpose Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC). Methods GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only. The presence of GSTM1:ASK1 protein-protein interaction in ccRCC tissue samples was analyzed by methods of immunoprecipitation and immunoblot. Results We noted an increased risk of RCC development in carriers of GSTM1-null and GSTP1-variant genotype (P<0.05). On the contrary, survival analysis indicated shorter overall survival for patients with ccRCC with GSTM1-active genotype (P = 0.026). Furthermore, patients with ccRCC with GSTM1-active genotype had significantly higher hazard ratio (P<0.05), in analyzed regression models, compared with the carriers of GSTM1-null genotype. Finally, the presence of GSTM1:ASK1 protein-protein interaction was found in all RCC tissue samples studied. Conclusions Carriers of GSTM1-null and GSTP1-variant genotypes are in increased risk of RCC development. On the contrary, GSTM1-null genotype is associated with favorable postoperative prognosis in ccRCC. The possible molecular mechanism underlying the role of GSTM1 protein in RCC progression might be the presence of GSTM1:ASK1 protein-protein interaction. Hence, determination of GSTM1-genotype might serve as a valuable indicator in both RCC risk assessment and postoperative prognosis. © 2017 Elsevier Inc.