The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C
Abstract Background Despite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the...
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2021-02-01
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Online Access: | https://doi.org/10.1186/s12876-021-01654-3 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arthur Ivan N. Oliveira Fernanda M. Malta Patricia Momoyo Y. Zitelli Ana Paula M. Salles Michele S. Gomes-Gouvea Ana Catharina S. Nastri Joao Renato R. Pinho Flair J. Carrilho Claudia P. Oliveira Maria Cássia Mendes-Corrêa Mario G. Pessoa Daniel F. Mazo |
spellingShingle |
Arthur Ivan N. Oliveira Fernanda M. Malta Patricia Momoyo Y. Zitelli Ana Paula M. Salles Michele S. Gomes-Gouvea Ana Catharina S. Nastri Joao Renato R. Pinho Flair J. Carrilho Claudia P. Oliveira Maria Cássia Mendes-Corrêa Mario G. Pessoa Daniel F. Mazo The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C BMC Gastroenterology Hepatitis C virus Hepatitis virus Genetic variation |
author_facet |
Arthur Ivan N. Oliveira Fernanda M. Malta Patricia Momoyo Y. Zitelli Ana Paula M. Salles Michele S. Gomes-Gouvea Ana Catharina S. Nastri Joao Renato R. Pinho Flair J. Carrilho Claudia P. Oliveira Maria Cássia Mendes-Corrêa Mario G. Pessoa Daniel F. Mazo |
author_sort |
Arthur Ivan N. Oliveira |
title |
The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C |
title_short |
The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C |
title_full |
The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C |
title_fullStr |
The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C |
title_full_unstemmed |
The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C |
title_sort |
role of pnpla3 and tm6sf2 polymorphisms on liver fibrosis and metabolic abnormalities in brazilian patients with chronic hepatitis c |
publisher |
BMC |
series |
BMC Gastroenterology |
issn |
1471-230X |
publishDate |
2021-02-01 |
description |
Abstract Background Despite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the studies. Methods This cross-sectional study enrolled 365 treatment-naïve patients with HCV and 134 healthy individuals. TM6SF2 (rs58542926 c.499C > T) and PNPLA3 (rs738409 c.444C > G) polymorphisms were evaluated regarding their association with clinical and laboratory data, histological liver steatosis and fibrosis, and with components of the metabolic syndrome. Results In HCV subjects, the frequencies of TM6SF2 CC and CT + TT were 89% and 11%, while PNPLA3 frequencies of CC and CG + GG were 51.4% and 48.6%. In the univariate logistic regression analysis, the TM6SF2 CT + TT genotype in HCV was associated with significant liver fibrosis (p = 0.047; OR 1.953; 95% CI 1.009–3.788). In comparison to the CT + TT genotype, the TM6SF2 CC genotype in HCV was associated with older age (p = 0.002), higher frequency of arterial hypertension (p = 0.032), obesity (p = 0.030), metabolic syndrome (p = 0.014) and lower total cholesterol levels (p = 0.036). The PNPLA3 GG subjects had lower body mass index than CG/ CC individuals (p = 0.047). None of the polymorphisms, or their combinations, was independently associated with hepatic steatosis or fibrosis. On the other hand, older age, lower serum levels of total cholesterol, and higher serum levels of alanine aminotransferase and alkaline phosphatase were associated with liver fibrosis in the multivariate logistic regression analysis. Conclusion In this evaluation of an admixed HCV population, neither TM6SF2 nor PNPLA3 polymorphisms were independently associated with hepatic steatosis or fibrosis. Other factors seem more influential than these specific polymorphisms in isolation. More studies are warranted to clarify the role of the TM6SF2 and PNPLA3 polymorphisms in Brazilians with HCV. |
topic |
Hepatitis C virus Hepatitis virus Genetic variation |
url |
https://doi.org/10.1186/s12876-021-01654-3 |
work_keys_str_mv |
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doaj-094ead3f78644ec69b06e298577979512021-02-23T10:35:38ZengBMCBMC Gastroenterology1471-230X2021-02-0121111010.1186/s12876-021-01654-3The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis CArthur Ivan N. Oliveira0Fernanda M. Malta1Patricia Momoyo Y. Zitelli2Ana Paula M. Salles3Michele S. Gomes-Gouvea4Ana Catharina S. Nastri5Joao Renato R. Pinho6Flair J. Carrilho7Claudia P. Oliveira8Maria Cássia Mendes-Corrêa9Mario G. Pessoa10Daniel F. Mazo11Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Department of Infectious Diseases, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Department of Infectious Diseases, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Division of Clinical Gastroenterology and Hepatology, LIM07, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP)Abstract Background Despite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the studies. Methods This cross-sectional study enrolled 365 treatment-naïve patients with HCV and 134 healthy individuals. TM6SF2 (rs58542926 c.499C > T) and PNPLA3 (rs738409 c.444C > G) polymorphisms were evaluated regarding their association with clinical and laboratory data, histological liver steatosis and fibrosis, and with components of the metabolic syndrome. Results In HCV subjects, the frequencies of TM6SF2 CC and CT + TT were 89% and 11%, while PNPLA3 frequencies of CC and CG + GG were 51.4% and 48.6%. In the univariate logistic regression analysis, the TM6SF2 CT + TT genotype in HCV was associated with significant liver fibrosis (p = 0.047; OR 1.953; 95% CI 1.009–3.788). In comparison to the CT + TT genotype, the TM6SF2 CC genotype in HCV was associated with older age (p = 0.002), higher frequency of arterial hypertension (p = 0.032), obesity (p = 0.030), metabolic syndrome (p = 0.014) and lower total cholesterol levels (p = 0.036). The PNPLA3 GG subjects had lower body mass index than CG/ CC individuals (p = 0.047). None of the polymorphisms, or their combinations, was independently associated with hepatic steatosis or fibrosis. On the other hand, older age, lower serum levels of total cholesterol, and higher serum levels of alanine aminotransferase and alkaline phosphatase were associated with liver fibrosis in the multivariate logistic regression analysis. Conclusion In this evaluation of an admixed HCV population, neither TM6SF2 nor PNPLA3 polymorphisms were independently associated with hepatic steatosis or fibrosis. Other factors seem more influential than these specific polymorphisms in isolation. More studies are warranted to clarify the role of the TM6SF2 and PNPLA3 polymorphisms in Brazilians with HCV.https://doi.org/10.1186/s12876-021-01654-3Hepatitis C virusHepatitis virusGenetic variation |