Impact of Oxidative Changes and Possible Effects of Genetics Polymorphisms of Glutathione S-Transferase in Diabetics Patients with Complications

Pancreatic β cells are more sensitive to cytotoxic stress than several other cells due to the expression of very low levels of antioxidant enzymes. Glutathione-S-transferase (GST) is a detoxification enzyme essential for a cellular protection against oxidative damage. Thus, the objective of this chapter is to verify the impact of the hypothesis of all effects of Glutathione S-transferase polymorphism in patients with diabetic complications. Diabetic nephropathy (DN) is the main secondary complication of diabetes mellitus (DM). Notably, the expression of GST genes has been described in different variations as ethnic populations. Some studies have suggested association between genetic polymorphism for GSTM1, GSTT1 and GSTP1 and DN, but others do not. The results are still inconsistent and, therefore, more studies are needed to be performed

Of genetic polymorphisms in susceptibility to diabetic nephropathy due to hemodynamic and endothelial changes

Submitted by Franciele Moreira ([email protected]) on 2020-01-07T15:00:02Z No. of bitstreams: 2 Dissertação - Laura Raniere Borges dos Anjos - 2018.pdf: 6751938 bytes, checksum: caaa71c5e1cec23d95dddefbd7241e6b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira ([email protected]) on 2020-01-08T12:46:32Z (GMT) No. of bitstreams: 2 Dissertação - Laura Raniere Borges dos Anjos - 2018.pdf: 6751938 bytes, checksum: caaa71c5e1cec23d95dddefbd7241e6b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2020-01-08T12:46:32Z (GMT). No. of bitstreams: 2 Dissertação - Laura Raniere Borges dos Anjos - 2018.pdf: 6751938 bytes, checksum: caaa71c5e1cec23d95dddefbd7241e6b (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-12-19Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESDiabetic nephropathy (DN) is the major microvascular complication of Diabetes mellitus (DM) and is among the leading causes of kidney disease. This pathology is important because of glomerular changes induced by imbalance of glucose homeostasis and high intraglomerular pressure. Studies indicate that diseases are influenced not only by the environment but also by genetic factors. Among the genetic determinants, the polymorphisms in the MTHFR and VEGF genes stand out. These genes are oriented towards the synthesis of the enzyme methylenetetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF), respectively. The MTHFR enzyme plays an important role in the processing and processing cycle of methionine. VEGF is an important protein involved in signaling that stimulates vasculogenesis and angiogenesis. Thus, the objective of this study was to perform a molecular evaluation of MTHFR C677T and VEGF -141 A → C single nucleotide polymorphisms (SNPs) in diabetic patients with microvascular complications caused by hemodynamic and endothelial changes in a Brazilian population. A total of 345 were genotyped for polymorphisms using PCR-RFLP. The advanced RStúdio environment was used for statistical analysis. The logistic regression of the gene polymorphism in the MTHFR gene increases the risk (OR = 2.57, p = 0.003) of the diabetic individual developing ND. The polymorphism in VEGF gene reveals a 3.74-fold risk for DN (p = 0.001) in the eventual condition of diabetic patient. When analyzing the association of clinical variables and polymorphism in the MTHFR gene, the results showed no correlation. The association of clinical variables with the VEGF gene polymorphism, the results indicated the same in creatinine, in GFR and in diastolic blood pressure. Clinical associations observe a mechanism underlying the role of polymorphisms in renal dysfunction. Results suggest that polymorphisms MTHFR gene confer susceptibility to ND in the patients with DM.A nefropatia diabética (DN) é a principal complicação microvascular do Diabetes mellitus (DM) e está entre as principais causas de doença renal. Essa patologia é causada por alterações glomerulares induzidas pelo desequilíbrio da homeostase da glicose e pela alta pressão intraglomerular. Estudos indicam que as doenças renais são influenciadas não apenas pelo ambiente, mas também por fatores genéticos. Entre os determinantes genéticos, destacam-se os polimorfismos nos genes MTHFR e VEGF. Esses genes fornecem instruções para a síntese da enzima metilenotetrahidrofolato redutase (MTHFR) e fator de crescimento endotelial vascular (VEGF), respectivamente. A enzima MTHFR desempenha um papel importante no ciclo do folato e processamento de metionina. O fator VEGF é uma importante proteína envolvida na sinalização que estimula a vasculogênese e a angiogênese. Assim, o objetivo deste estudo foi realizar uma avaliação molecular dos polimorfismos de nucleotídeo único (SNPs) MTHFR C677T e VEGF -141 A → C em pacientes diabéticos com complicação microvascular provocada por alterações hemodinâmicas e endoteliais, em uma população brasileira. Um total de 345 indivíduos foram genotipados, para os respectivos polimorfismos, utilizando PCR-RFLP. O ambiente avançado RSTúdio foi utilizado para as análises estatísticas. A regressão logística múltipla revelou que o polimorfismo no gene MTHFR aumenta o risco (OR = 2,57, p= 0,003) do indivíduo diabético desenvolver ND. O polimorfismo no gene VEGF revela um de risco de 3,74 vezes para o indivíduo saudável desenvolver ND (p=0,001), na eventual condição de paciente diabético. Ao analisar a associação de variáveis clínicas e o polimorfismo no gene MTHFR, os resultados não revelaram correlação. Na associação das variáveis clínicas com o polimorfismo no gene VEGF, os resultados indicaram alterações na creatinina, na TFG e na pressão arterial diastólica. As alterações clínicas observadas indicam um mecanismo subjacente ao papel dos polimorfismos na disfunção renal. Estes resultados sugerem que os polimorfismos no gene MTHFR conferem maior suscetibilidade à ND para indivíduos com DM

Association of the Polymorphism of GSTP1 with the Susceptibility to the Development of Schizophrenia

Schizophrenia is a complex mental illness characterized by the presence of symptoms such as hallucinations, delusions, catatonic behavior, cognitive impairment among others. Although the studies exceed 100 years, it is one of the mental illnesses less understood. Oxidative stress has been investigated as one of the potential stimulant factors in the development of schizophrenia. For the study of these relationships, the research focuses on polymorphisms of antioxidant enzymes, such as glutathione S-transferase (GST), an important phase II detoxification enzyme. In this context, the aim of the study is to associate the GSTP1 gene polymorphism with the susceptibility to the development of schizophrenia through a case-control study. The knowledge of the genetic predisposition comes as a support for the understanding of schizophrenia, allowing later the establishment of markers of susceptibility to the disease, which when identified will allow the taking of preventive measures and better targeting of the treatment. Methods: For the analysis of the polymorphisms using the PCR-RFLP technique, the samples collected at the Brain Institute Clinic were divided into two groups, case and control, for later study of the heterozygous genotypes (Ile / Val), wild homozygote (Ile / Ile) and mutant homozygote (Val / Val). Results: There was no statistically significant correlation between GSTP1 polymorphism and the risk of developing schizophrenia. Conclusions: In this sense, more studies should be carried out in search of more consistent results, thus allowing a more accurate correlation regarding the role of this polymorphism with the susceptibility to schizophrenia

Molecular Analysis of the Glutathione S-Transferase System in Patients with Depression

Depression is defined as a mood disorder in which changes in temperament occur making the patient sad, lacking energy and, at a severe stage, with suicidal thoughts. Depression is a multifactorial tantrum that may be associated with changes in neurotransmitters, social or genetic factors. It is suggested that oxidative stress may be associated with worsening of depression in patients not treated with antidepressants. In addition, it is known that oxidative stress is favored in situations where the individual presents a compromise in the function of antioxidant enzymes, such as GSTP1. The objective of the present study was to verify if the GSTP1 gene polymorphism confers genetic susceptibility to depression. Methods: PCR-RFLP technique was used to analyze polymorphisms. The samples were collected at the Brain Institute Clinic were divided into two groups, case and control, for later study of the heterozygous genotypes (Ile / Val), wild homozygote (Ile / Ile) and mutant homozygote (Val / Val). The results suggest that there was no statistically significant correlation between GSTP1 polymorphism and the risk of developing depression (p = 0.1835). Conclusions: In this sense, more studies should be carried out in search of more consistent results, thus allowing more accurate correlation regarding the role of this polymorphism with the susceptibility to depression

Clinical data and risk factors for diabetic nephropathy in Brazilian central population

This article describes data set of the profile of patients diagnosed with Diabetic Nephropathy (DN) undergoing hemodialysis and followed-up by Hemodialysis Service in medical centers in Goiânia, Go, Brazil. These data describe specifically the demographic, clinical, and lifestyle variables of 101 patients. In addition, these data provide detailed clinical associations about the profile of patients diagnosed with DN and which are made publicly available to enable critical or extended analyzes. For further interpretation of the data presented in this article, see the research article: Do GST polymorphisms influence in the pathogenesis of diabetic nephropathy? (Lima et al., 2018)

Popularization of Science: Demystifying the Central Dogma of Molecular Biology

This extension project was presented during the XII edition of the Cultural and Scientific Movement of Aparecida de Goiânia, Goiás, Brazil (MOCCA). The objective was to promote the basic scientific knowledge on the flow of genetic information from experimentation by illustrative methods. Each participant answered a questionnaire to assess their prior knowledge of the topic. He was then directed to a monitor that accompanied him, through the interactive environment, presenting illustrations with models, panels, three-dimensional models, as well as the accomplishment of the simple extraction of DNA from a fruit. At the end, the same questionnaire was reapplied. The comparative analysis of the participant’s performance in the questionnaire before and after the activities showed that interactive and illustrative practical approaches contributed positively to the better understanding of the content suggesting that this methodology can be incorporated into the teaching-learning process