Do GSTM1 and GSTT1 polymorphisms influence the risk of developing mitochondrial diseases in a Tunisian population?
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
Authors: Ghorbel, Raouia; Ben Salah, Ghada; Ghorbel, Rania; Ben Mahmoud, Afif; Chamkha, Imen; Mkaouar-Rebai, Emna; Ammar-Keskes, Leila; Fakhfakh, Faiza
Abstract
Mitochondria play an essential role to supply the cell with metabolic energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As a consequence, they are also the primary source of cellular reactive oxygen species (ROS) which can cause oxidative damage of individual respiratory chain complexes. Indeed, affected OXPHOS subunits result in decreases in ATP production and increases in ROS formation which generate oxidative phosphorylation deficiency leading to mitochondrial dysfunctions. It has been suggested that ROS play a vital role in the pathogenesis of mitochondrial diseases. To the best of our knowledge, this is the first study which aimed to investigate the genetic variant effect of the antioxidant enzymes GSTM1 and GSTT1 on mitochondrial disease among a Tunisian population. In this report, 109 patients with mitochondrial disease and 154 healthy controls were genotyped by multiplex PCR amplification, and data were analyzed by SPSS v20 software. The results showed that GSTM1 null genotype was found to be associated with mitochondrial disease with a protective effect; however, no significant association of GSTT1 polymorphism with mitochondrial disease risk was revealed. But, interestingly, our findings highlight that GSTM1 active and GSTT1 null genotype combination increased by three fold the risk of developing mitochondrial disease with p (c) = 0.020, notably mitochondrial myopathy with p (c) = 0.046 and Leigh syndrome with p (c) = 0.042. In conclusion, this study suggests that GSTM1 active and GSTT1 null genotype combination might be a risk factor in developing mitochondrial disease.
GSTM1 and GSTT1 null polymorphism and antioxidant levels in oral submucous fibrosis, leukoplakia and oral cancer patients among a South Indian Population
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY
Authors: Madhulatha, G.; Das, Satrupa; Venkateswarlu, N.; Pujar, Akhilesh; Jyothy, Akka; Munshi, Anjana
Abstract
Objective: We investigated the null polymorphism in GSTM1 and GSTT1 genes and the antioxidant levels in oral submucous fibrosis (OSMF), leukoplakia and oral cancer patients along with healthy controls in a South Indian cohort. Methods: Genotyping was done using multiplex PCR and the antioxidant levels were estimated using biochemical methods Association between genotypes and different diseased states was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis and for antioxidant levels student's t-test was used. Results: The relative risk for GSTM1 and GSTT1 gene polymorphisms was statistically insignificant for the 3 patient groups vs. controls. Comparing the frequency of the null genotypes between the groups of patients only GSTM1 polymorphism revealed a significant difference between OSMF & oral cancer subjects (p = 0.02). Further, analysis of the antioxidant parameters shows ceruloplasmin levels to be significantly elevated between patient groups and controls and among OSMF vs. cancer patients (p < 0.05). Similarly, malondialdehyde and glutathione levels were found to be significantly elevated among cancer and both cancer and leukoplakia subjects respectively in comparison with controls (p < 0.05). Analysis between the patient groups revealed glutathione levels to be significantly elevated between OSMF vs. cancer patients and cancer vs. leukoplakia patients (p < 0.05). Conclusion: In conclusion, this study finds GSTM1 null genotype and antioxidants (ceruloplasmin and glutathione levels) to be significantly higher in oral cancers than in precancerous lesions, and suggesting that they might be associated with the malignant transformation of the oral precancers. (C) 2017 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.