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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2021.tde-07072021-105858
Document
Author
Full name
Arthur Ivan Nobre Oliveira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2021
Supervisor
Committee
Pessôa, Mário Guimarães (President)
Cheinquer, Hugo
Ferraz, Maria Lúcia Cardoso Gomes
Rodriguez, Tomás Navarro
Title in Portuguese
Influência dos polimorfismos nos genes Patatin-like Phospholipase Domain Containing 3 (PNPLA3) e Transmembrane 6 Superfamily Member 2 (TM6SF2) na hepatite C crônica
Keywords in Portuguese
Cirrose hepática.
Hepatite C crônica
Patatin like phospholipase domain-containing 3
Polimorfismo de nucleotídeo único
Transmembrane 6 Superfamily Member 2
Abstract in Portuguese
Introdução: Apesar dos conhecimentos crescentes a respeito dos polimorfismos dos genes TM6SF2 e PNPLA3, a sua influência no espectro da da doença hepática crônica pelo vírus da hepatite C (HCV) ainda não está totalmente definida. Além disso, populações miscigenadas, como a brasileira, não foram incluídas na maioria dos estudos. O objetivo desde estudo foi descrever a prevalência destes polimorfismos em brasileiros com hepatite C crônica e avaliar a sua associação com fibrose hepática e outros componentes da síndrome metabólica. Métodos: Estudo transversal e unicêntrico que avaliou 365 pacientes com hepatite C crônica, virgens de tratamento, e 134 indivíduos saudáveis. Os polimorfismos do PNPLA3 (rs738409 c.444C>G) e do TM6SF2 (rs58542926 c.449C>T) foram avaliados. Resultados: Entre os saudáveis, as frequências do TM6SF2 CC e CT + TT foram de 93.28% e 6.72%, respectivamente; estas foram 88.95 % e 11.05% em pacientes com o HCV. Em relação ao PNPLA3, dentre os saudáveis, as frequências de CC e CG + GG foram 49.25% e 50.74%, respectivamente; estas foram 51.37% e 48.63% entre os pacientes com HCV. Em pacientes com hepatite C, pela análise univariada, os genótipos TM6SF2 CT + TT foram associados com fibrose hepática significativa (p=0,0471, OR 1,953, IC95% 1,009-3,788) em comparação com genótipo CC, enquanto este foi associado com idade mais avançada (p=0,0024), maior frequência de hipertensão arterial sistêmica (p=0,0327), obesidade (p=0,0309), síndrome metabólica (p=0,0141) e níveis mais elevados de colesterol total (p=0.0360), em comparação aos genótipos CT + TT. Portadores de VHC com o PNPLA3 GG tiveram menor IMC (p=0,0469) e menor frequência de síndrome metabólica (p=0,0137) do que os indivíduos CG + CC. Nenhum dos polimorfismos foi associado de forma independente com esteatose hepática ou fibrose. Conclusões: A presença dos genótipos TM6SF2 CT + TT foi associada com fibrose hepática significativa em pacientes com HCV, o mesmo não sendo observado para os polimorfismos do PNPLA3
Title in English
Influence of polymorphisms on the Patatin-like Phospholipase Domain Containing 3 (PNPLA3) and Transmembrane 6 Superfamily Member 2 (TM6SF2) genes in chronic hepatitis C
Keywords in English
Hepatite C chronic
Liver cirrhosis
Patatin like phospholipase domain-containing 3
Polymorphism single nucleotide
Transmembrane 6 Superfamily Member 2
Abstract in English
Introduction: Despite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms, their influence in the spectrum of HCV liver disease is not yet fully defined. Moreover, admixed populations, such as Brazilians, were not included in most studies. The aim of this study was to describe the prevalence of these polymorphisms in Brazilians with chronic hepatitis C, and to assess their association with liver fibrosis and other components of the metabolic syndrome. Methods: This single center cross-sectional study enrolled 365 patients with chronic hepatitis C, naïve for antiviral therapy, and 134 healthy individuals. PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) polymorphisms were evaluated. Results: In healthy subjects, the frequencies of TM6SF2 CC and CT + TT were 93.28% and 6.72%, respectively; these were 88.95 % and 11.05% in patients with HCV. Regarding PNPLA3, in healthy subjects, the frequencies of CC and CG + GG were 49.25% and 50.74%, respectively; these were 51.37% and 48.63% in patients with HCV. In the univariate analysis, TM6SF2 CT + TT genotypes in HCV was associated with significant liver fibrosis among patients with HCV (p=0.0471, OR 1.953, 95%CI 1.009-3.788). TM6SF2 CC genotype in patients with HCV was associated with older age (p=0,0024), higher frequency of arterial hypertension (p=0.0327), obesity (p=0.0309), metabolic syndrome (p=0.0141), and total cholesterol (p=0.0360), in comparison to CT + TT genotype. PNPLA3 GG subjects had lower BMI (p=0,0469) and less metabolic syndrome (p=0.0137) than CG / CC individuals. None of the polymorphisms were independently associated with hepatic steatosis or fibrosis. Conclusions: The presence of the TM6SF2 CT + TT genotype was associated with significant liver fibrosis in patients with HCV, but not the PNPLA3 polymorphisms
 
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Publishing Date
2021-07-07
 
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