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PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC

BACKGROUND: The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent major genetic risk factors for progressive liver injury in nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD) and chronic viral hepatitis. The aim of this st...

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Autores principales: Kruk, Beata, Liebe, Roman, Milkiewicz, Małgorzata, Wunsch, Ewa, Raszeja-Wyszomirska, Joanna, Lammert, Frank, Milkiewicz, Piotr, Krawczyk, Marcin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117000/
https://www.ncbi.nlm.nih.gov/pubmed/30161167
http://dx.doi.org/10.1371/journal.pone.0202942
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author Kruk, Beata
Liebe, Roman
Milkiewicz, Małgorzata
Wunsch, Ewa
Raszeja-Wyszomirska, Joanna
Lammert, Frank
Milkiewicz, Piotr
Krawczyk, Marcin
author_facet Kruk, Beata
Liebe, Roman
Milkiewicz, Małgorzata
Wunsch, Ewa
Raszeja-Wyszomirska, Joanna
Lammert, Frank
Milkiewicz, Piotr
Krawczyk, Marcin
author_sort Kruk, Beata
collection PubMed
description BACKGROUND: The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent major genetic risk factors for progressive liver injury in nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD) and chronic viral hepatitis. The aim of this study was to find out whether these variants have a detrimental impact on the progression of chronic liver disease in patients with prolonged cholestasis induced by primary sclerosing cholangitis (PSC). METHODS: We prospectively recruited 178 PSC patients (112 male, age range 17–75 years, 55 with liver cirrhosis, 94 with ulcerative colitis, 48 transplanted during follow-up). PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms were genotyped using dedicated TaqMan assays. Associations between genotypes, biochemical and clinical phenotypes were analyzed using contingency tables. RESULTS: Allele and genotype distribution of both variants were consistent with Hardy-Weinberg equilibrium. No significant differences in the genotype distribution of PNPLA3 (P = 0.90) or TM6SF2 (P = 0.72) were observed between patients with cirrhosis and patients without cirrhosis. Serum liver enzyme activities were not modified by the presence of PNPLA3 (ALT P = 0.88, AST P = 0.77) or TM6SF2 (ALT P = 0.92, AST P = 0.49) risk variants. Increasing number of risk alleles had no impact on serum liver enzyme activities, as demonstrated by a separate analysis of patients carrying 0 (n = 99), 1 (n = 64), 2 (n = 12) or 3 (n = 3) risk alleles (P>0.05). No impact of PNPLA3 or TM6SF2 risk variants was detectable in patients with PSC and ulcerative colitis, and none of the variants increased the odds of transplantation. CONCLUSIONS: Neither PNPLA3 nor TM6SF2 polymorphisms seem to contribute significantly towards an increased risk for deterioration of liver function in patients with PSC. These results underscore the divergent mechanisms of liver damage in cholestatic conditions as compared to metabolic and viral liver diseases.
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spelling pubmed-61170002018-09-16 PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC Kruk, Beata Liebe, Roman Milkiewicz, Małgorzata Wunsch, Ewa Raszeja-Wyszomirska, Joanna Lammert, Frank Milkiewicz, Piotr Krawczyk, Marcin PLoS One Research Article BACKGROUND: The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent major genetic risk factors for progressive liver injury in nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD) and chronic viral hepatitis. The aim of this study was to find out whether these variants have a detrimental impact on the progression of chronic liver disease in patients with prolonged cholestasis induced by primary sclerosing cholangitis (PSC). METHODS: We prospectively recruited 178 PSC patients (112 male, age range 17–75 years, 55 with liver cirrhosis, 94 with ulcerative colitis, 48 transplanted during follow-up). PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms were genotyped using dedicated TaqMan assays. Associations between genotypes, biochemical and clinical phenotypes were analyzed using contingency tables. RESULTS: Allele and genotype distribution of both variants were consistent with Hardy-Weinberg equilibrium. No significant differences in the genotype distribution of PNPLA3 (P = 0.90) or TM6SF2 (P = 0.72) were observed between patients with cirrhosis and patients without cirrhosis. Serum liver enzyme activities were not modified by the presence of PNPLA3 (ALT P = 0.88, AST P = 0.77) or TM6SF2 (ALT P = 0.92, AST P = 0.49) risk variants. Increasing number of risk alleles had no impact on serum liver enzyme activities, as demonstrated by a separate analysis of patients carrying 0 (n = 99), 1 (n = 64), 2 (n = 12) or 3 (n = 3) risk alleles (P>0.05). No impact of PNPLA3 or TM6SF2 risk variants was detectable in patients with PSC and ulcerative colitis, and none of the variants increased the odds of transplantation. CONCLUSIONS: Neither PNPLA3 nor TM6SF2 polymorphisms seem to contribute significantly towards an increased risk for deterioration of liver function in patients with PSC. These results underscore the divergent mechanisms of liver damage in cholestatic conditions as compared to metabolic and viral liver diseases. Public Library of Science 2018-08-30 /pmc/articles/PMC6117000/ /pubmed/30161167 http://dx.doi.org/10.1371/journal.pone.0202942 Text en © 2018 Kruk et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kruk, Beata
Liebe, Roman
Milkiewicz, Małgorzata
Wunsch, Ewa
Raszeja-Wyszomirska, Joanna
Lammert, Frank
Milkiewicz, Piotr
Krawczyk, Marcin
PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC
title PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC
title_full PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC
title_fullStr PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC
title_full_unstemmed PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC
title_short PNPLA3 p.I148M and TM6SF2 p.E167K variants do not predispose to liver injury in cholestatic liver diseases: A prospective analysis of 178 patients with PSC
title_sort pnpla3 p.i148m and tm6sf2 p.e167k variants do not predispose to liver injury in cholestatic liver diseases: a prospective analysis of 178 patients with psc
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117000/
https://www.ncbi.nlm.nih.gov/pubmed/30161167
http://dx.doi.org/10.1371/journal.pone.0202942
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