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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2019.tde-16102019-092209
Document
Author
Full name
Leevan José Sousa Leite
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2019
Supervisor
Committee
Santos, Jose Eduardo Tanus dos (President)
Carneiro, Fernando Silva
Luizon, Marcelo Rizzatti
Santos, Milena Jorge Simões Flória Lima
Title in Portuguese
Polimorfismos do gene PDE5A e as suas implicações sobre a resposta ao sildenafil na disfunção erétil
Keywords in Portuguese
Disfunção erétil
Fosfodiesterase tipo 5
Polimorfismos
Polimorfismos no gene PDE5A
Abstract in Portuguese
A disfunção erétil (DE) é considerada uma manifestação funcional e estrutural anormal que afeta a capacidade de atingir ou manter a ereção peniana suficiente para alcançar uma relação sexual satisfatória. Os fatores de riscos que podem levar ao desenvolvimento de DE, sâo: doenças cardiovasculares, diabetes Mellitus, tabagismo, alcoolismo, medicamentos. O sildenafil, como outros inibidores de PDE-5, é um fármaco de primeira linha de escolha para o tratamento da DE. A fosfodiesterase tipo 5 regula a via NO-GMPc por meio de uma reação de hidrólise, transformando o GMPc em GMP, o qual não apresenta capacidade de relaxar o músculo. Com a inibição da PDE-5 aumenta a biodisponibilidade de GMPc, favorecendo ao relaxamento do músculo liso e por fim facilitando a ereção. Apesar dos inibidores de PDE-5 serem eficazes no tratamento de DE, cerca de 30 a 40% dos pacientes não respondem ao tratamento. Estudos mostram que a presença de alelos variantes de polimorfismos no gene PDE5A podem influenciar na resposta ao sildenafil. Tendo base nisso, a hipótese do nosso trabalho é que a presença de alelos variantes de polimorfismos do gene PDE5A: rs2389866, rs3733526 e rs13124592 estão associados a variações na resposta ao sildenafil. Para o estudo foram recrutados pacientes com disfunção erétil clínica (DEC, n=71) e pós prostatectomia ( DEPP, n=71) do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, nas quais foram aplicados o questionário IIEF (Índice internacional de função erétil, IIEF - sigla em inglês) e coletadas amostras de sangue para realização de genotipagem pela técnica de Real Time - PCR. De acordo com os resultados o alelo variante "C" do polimorfismo rs2389866 está associado a pior resposta ao sildenafil nos pacientes com DEPP
Title in English
Influence of PDE5A gene polymorphism on the response to erectile dysfunction therapy with sildenafil
Keywords in English
Erectile dysfunction
IIEF
PDE5A
Phosphodiesterase type 5
Polymorphism
Abstract in English
Erectile dysfunction (ED) is considered a functional and structural abnormal manifestation that affects the capacity of achieve and maintain a sufficient penile erection in order to have a satisfactory sexual relation. The risk factors for the erectile dysfunction development are: cardiovascular diseases, diabetes Mellitus, smoking, alcoholism, medicines. Sidenafil as others PDE-5 inhibitors are first line drugs of choice for erectile dysfunction. Phosphodiesterase type 5 regulates the way NO-GMPc converts GMPc in GMP, that is incapable to relax the muscle, through a hydrolysis reaction. With PDE-5 inhibition, the GMPc bioavailability increases smooth muscle relaxation finally facilitating the erection. Although PDE-5 inhibitors are the most effective in erectile dysfunction treatment about 30 to 40% of the patients are unresponsive to the treatment. Studies demonstrate that alleles variants of polymorphism present in gene PDE5A can influence sildenafil response. Based on that, our work hypothesis is that the presence of gene PDE5A alleles variants of polymorphism (rs2389866, rs3733526 and rs13124592) are associated to the variation in sildenafil response. For the study were enrolled patients with clinical erectile dysfunction (CED, n=71) and erectile dysfunction post-prostatectomy (EDPP, n=71) from Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. The International Index of Erectile Function (IIEF) was applied for those patients and blood samples were collected to perform the genotyping by the Real Time - PCR technique. According to the results, the variant "C" allele of polymorphism rs2389866 is associated with a worse response to sildenafil in patients with EDPP
 
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Publishing Date
2019-11-12
 
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