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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2019.tde-17042019-092036
Document
Author
Full name
Sylene Coutinho Rampche de Carvalho
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Oliveira, Claudia Pinto Marques Souza de (President)
Moura, Patricia Muniz Mendes Freire de
Ono, Suzane Kioko
Sabbaga, Jorge
Title in Portuguese
Avaliação de polimorfismos no gene do fator de crescimento endotelial vascular (VEGF) e da metilenotetrahidrofolato redutase (MTHFR) em pacientes com carcinoma hepatocelular e infecção pelo vírus da hepatite C
Keywords in Portuguese
Carcinoma hepatocelular
Cirrose hepática
Fator A do crescimento do endotélio
Fígado
Hepatite C
Polimorfismo genético
Abstract in Portuguese
INTRODUÇÃO: A cirrose hepática é fator de risco para o Carcinoma hepatocelular (CHC) e no Brasil, a etiologia de doença hepática crônica mais frequente associada ao CHC é a infecção crônica pelo vírus da hepatite C (VHC). Angiogênese e deficiência de folato podem estar associados ao risco de CHC. Deste modo, os polimorfismos de genes relacionados com esses processos o VEGF e MTHFR em doentes com hepatite C crônica e CHC podem conduzir a marcadores genéticos para CHC na infecção por HCV.OBJETIVOS: Avaliar os polimorfismos G634C (rs2010963), C460T (rs833061), C936T (rs3025039) do gene do VEGF e polimorfismos C677T (rs1801133) e C1298A (1801131) da MTHFR, em pacientes brasileiros com CHC e infecção crônica pelo VHC . PACIENTES E MÉTODOS: Foram incluídos 119 pacientes com seguimento de CHC e VHC na clínica de hepatologia do HUOC / UPE e do IFP-PE, Brasil. Este estudo teve aprovação do comitê de ética e os pacientes assinaram o formulário de consentimento. Todos os pacientes tiveram diagnóstico de VHC por PCR e CHC por ressonância magnética e / ou tomografia.RESULTADOS: Dentre os indivíduos com CHC, 70,59% foram homens. A média de idade dos participantes foi de 62,3 anos. De acordo com a classificação de Child-Pugh, ficaram assim distribuídos: A 60,9%; B 36,5%; C 2,6%. O tamanho do tumor médio foi de 4,4 cm. Sendo que 52,10% foi multinodular. Foi feita uma análise de associação com os genes MTHFR e VEGF e características do tumor nos pacientes com CHC infectados cronicamente com VHC. Os alelos C da MTHFR (rs1801131) e da VEGF (rs2010963) foram associados com a proteção para o desenvolvimento da forma multinodular, e o alelo T da MTHFR (rs1801133) foi associado a fator de risco para desenvolvimento da forma multinodular p=0,04 OR 1,835 IC (1,0223,297). Foram realizadas análises multivariadas, incluindo-se no modelo o sexo masculino e a idade como potenciais fatores de confusão, o gene VEGF genótipo CC (rs2010963) foi um fator independente associado à proteção ao desenvolvimento de tumores multinodulares. Foi também realizada uma análise de sobrevivência estratificada pelos genótipos MTHFR (rs1801131), MTHFR (rs1801133) e VEGF (rs2010963), mas não foram observados resultados significativos. CONCLUSÕES: Foi observado que os genes MTHFR e VEGF tem influência na forma de apresentação uni ou multinodular do tumor
Title in English
Polymorphisms in the vascular endothelial growth factor (VEGF) and methylenetetrahydrofolate reductase (MTHFR) gene in patients with hepatocellular carcinoma and hepatitis C virus infection
Keywords in English
Carcinoma hepatocellular
Hepatitis C
Liver
Liver cirrhosis
Polymorphism genetic
Vascular endothelial growth factor A
Abstract in English
BACKGROUND: Hepatic cirrhosis is a risk factor for hepatocellular carcinoma (HCC) and in Brazil, the most frequent chronic liver disease associated with HCC is chronic hepatitis C virus (HCV) infection. Angiogenesis and folate deficiency may be associated with the risk of HCC. Thus, gene polymorphisms related to such processes VEGF and MTHFR in patients with chronic hepatitis C and HCC may lead to genetic markers for HCC in HCV infection. OBJECTIVES: To evaluate the polymorphisms G634C (rs2010963), C460T (rs833061), C936T (rs3025039) of the VEGF gene and polymorphisms C677T (rs1801133) and C1298A (1801131) of MTHFR, in Brazilian patients with HCC and chronic HCV infection. PATIENTS AND METHODS: A total of 119 patients with HCC and HCV follow-up were included in the HUOC / UPE and IFP-PE hepatology clinic in Brazil. This study was approved by the ethics committee and the patients signed the consent form. All patients had a diagnosis of HCV by PCR and HCC by magnetic resonance and / or tomography. RESULTS: Among the individuals with HCC, 70.59% were men. The mean age of participants was 62.3 years. According to the Child-Pugh classification, the following were distributed: At 60.9%; B 36.5%; C 2.6%. The mean tumor size was 4.4 cm. Being that 52.10% was multinodular. An association analysis was made with the MTHFR and VEGF genes and tumor characteristics in HCC patients chronically infected with HCV. The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with developmental protection of the multinodular form, and the MTHFR T allele (rs1801133) was associated with a risk factor for development of the multinodular form p = 0, 04 OR 1,835 IC (1,0223,297). Multivariate analyzes, including male gender and age as potential confounders, were performed in the VEGF gene genotype CC (rs2010963), which was an independent factor associated with the protection of the development of multinodular tumors. A survival analysis stratified by the MTHFR (rs1801131), MTHFR (rs1801133) and VEGF (rs2010963) genotypes was also performed, but no significant results were observed. CONCLUSIONS: It was observed that the MTHFR and VEGF genes have influence on the uni or multinodular presentation of the tumor
 
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Publishing Date
2019-04-17
 
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