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Master's Dissertation
DOI
https://doi.org/10.11606/D.22.2020.tde-17122019-172604
Document
Author
Full name
Anderson Heiji Lima Miyazaki
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2019
Supervisor
Committee
Lacchini, Riccardo (President)
Luizon, Marcelo Rizzatti
Pinheiro, Lucas Cézar
Santos, Milena Jorge Simões Flória Lima
Title in Portuguese
Polimorfismos genéticos da Alanina--Glioxilato Aminotransferase 2 (AGXT2) associados à disfunção erétil e marcadores de resposta aos iPDE-5
Keywords in Portuguese
Disfunção erétil
Óxido nítrico
Polimorfismos genéticos
SDMA
Abstract in Portuguese
Disfunção Erétil (DE) é caracterizada pela incapacidade de obter ou manter uma ereção suficiente para que ocorra atividade sexual satisfatória. Uma das principais características da DE está relacionada ao possível déficit na produção de Óxido Nítrico (NO) no corpo humano. O NO é produzido através da L-arginina, via Óxido Nítrico Sintase neuronal, endotelial e induzível (nNOS, eNOS e iNOS). As dimetilargininas assimétrica (ADMA) e a simétrica (SDMA) são formas metiladas da L-arginina e atuam como agentes inibidores das NOS, portanto os níveis aumentados de ADMA e SDMA estão associados a menor produção de NO. Uma das principais enzimas responsáveis pela degradação de ADMA e SDMA é a AGXT2, codificada pelo gene homônimo. Estudos têm relacionado polimorfismos genéticos da AGXT2 a doenças cardiovasculares e todo o contexto do NO, podendo ser utilizados como marcadores para o risco de desenvolvimento de DE. Os objetivos deste estudo visam relacionar polimorfismos genéticos da AGXT2 (rs37369 e rs16899974) ao risco para desenvolvimento de DE e ao resultado da terapia medicamentosa com inibidores da fosfodiesterase 5 (iPDE-5). Trata-se de um estudo de dois braços, sendo o primeiro um estudo caso-controle e outro apenas com os pacientes em uso de iPDE-5, avaliando a resposta a essa classe de fármacos. A função erétil dos voluntários desta pesquisa foi avaliada através da escala Índice Internacional de Função Erétil (IIEF). Os genótipos foram obtidos por PCR em tempo real. Foram encontrados associações significativas entre os marcadores genéticos e a resposta ao sildenafil e aos níveis de nitrito e ADMA. Quanto ao estudo caso-controle não foram encontrados associações significativas para este estudo
Title in English
Genetic polymorphysms of alanine - Glyoxylate Aminotransferase 2 (AGXT2) associated with erectile dysfunction and response markers to iPDE-5
Keywords in English
Erectile dysfunction
Genetic polymorphisms
Nitric oxide
SDMA
Abstract in English
Erectile Dysfunction (ED) is characterized by the inability to obtain or maintain an erection sufficient for satisfactory sexual activity to occur. One of the main features of ED is related to the possible deficit in the production of nitric oxide (NO) in the human body. NO is produced through L-arginine via neuronal, endothelial and inducible nitric oxide synthase (nNOS, eNOS and iNOS). Asymmetric (ADMA) and symmetrical (SDMA) dimethylarginines are methylated forms of L-arginine and act as NOS inhibitory agents, so increased levels of ADMA and SDMA are associated with decreased NO production. One of the main enzymes responsible for the degradation of ADMA and SDMA is AGXT2, encoded by the homonymous gene. Studies have linked genetic polymorphisms of AGXT2 to cardiovascular diseases and the entire context of NO, and can be used as markers for the risk of developing ED. The objectives of this study were to correlate AGXT2 genetic polymorphisms (rs37369 and rs16899974) with the risk for developing ED and the outcome of the drug therapy with phosphodiesterase 5 inhibitors (iPDE-5). It is a two-arm study, the first being a case-control study and the other only with patients using iPDE-5, evaluating the response to this class of drugs. The erectile function of the volunteers of this research was evaluated through the International Index of Erectile Function (IIEF) scale. Genotypes were obtained by real-time PCR. Significant associations were found between genetic markers and response to sildenafil and levels of nitrite and ADMA. Regarding the case-control study, no significant associations were found for this study
 
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Publishing Date
2020-02-03
 
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