Variantes polimórficas em genes de detoxificação celular e suas relações com o desenvolvimento da esclerose lateral amiotrófica

• Ano de defesa: 2020
• Autor(a) principal: Santos, Kamilla de Faria
• Orientador(a): Reis, Angela Adamski da Silva
• Banca de defesa: Reis, Angela Adamski da Silva, Bailão, Alexandre Melo, Souza, Guilherme Rocha Lino de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Programa de Pós-graduação em Genética e Biologia Molecular (ICB)
• Departamento: Instituto de Ciências Biológicas - ICB (RG)
• País: Brasil
• Palavras-chave em Português: ELA; Polimorfismo genético; Glutationa S-transferase; GSTM1; GSTT1
• Palavras-chave em Inglês: ALS; Genetic polymorphism; Glutathione S-transferase
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::GENETICA::GENETICA HUMANA E MEDICA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/12473

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons, leading to progressive muscular atrophy. Studies suggest the relationship of the disease with environmental and genetic factors, and the involvement of mechanisms, such as oxidative stress, with neuronal degeneration. However, the body has several ways to promote cellular detoxification against harmful compounds. The Glutathione S-transferase (GST) family consists of multifunctional enzymes that act on cell detoxification and elimination of various substances, including oxidative stress products. Among the human cytosolic classes of the GST family, two isoenzymes are highlighted: GSTM1 and GSTT1, both encoded by genes of the same name, these genes have a total deletion polymorphism that results in the absence of enzymatic activity. Therefore, the objective of the present study was to evaluate the deletion polymorphisms in GSTM1 and GSTT1 genes and their association with the risk of developing ALS. A case-control study was conducted, including 101 patients diagnosed with ALS and 119 individuals without diagnosis of neurodegenerative diseases. Peripheral blood samples were collected from both groups and subjected to DNA extraction and subsequent genotyping. The polymorphisms were genotyped by the multiplex real - time PCR (qPCR) technique, with the definition of the null and present genotypes by analysis of the melting curves produced after the amplification. Clinical and demographic data were collected from medical records and questionnaires, including topics such as cigarette use, alcohol intake, age of diagnosis, physical activity practice, occupational history, among others. Among the groups analyzed, alcohol consumption was predominant in patients with ALS, with a significant difference between the case and control groups (p=0.01). However, there was no association of GSTM1 (p=0.85), GSTT1 (p=0.90) deletion polymorphisms and their possible genotypic combinations with the risk of developing ALS. The relationship of polymorphisms with the clinical and demographic profile of patients with the disease was also performed. In this analysis, there was a significant difference in the GSTM1-present genotype with the variables: environmental exposure and smoking (p = 0.02 and 0.03, respectively), in the GSTT1-present genotype with a history of neurodegenerative disease in the family (p=0.01), while the double genotype present also showed a significant difference with the family history of neurodegenerative disease (p=0.02). In this context, the results found in this study demonstrate the non-association of GSTM1 and GSTT1 deletion polymorphisms with the development of ALS.