The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.

<h4>Background</h4>An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predispositio...

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Autores principales:	Hans Dieter Nischalke, Cordula Berger, Carolin Luda, Thomas Berg, Tobias Müller, Frank Grünhage, Frank Lammert, Martin Coenen, Benjamin Krämer, Christian Körner, Natascha Vidovic, Johannes Oldenburg, Jacob Nattermann, Tilman Sauerbruch, Ulrich Spengler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7eb1b9d661c04ff89accb593ab8daa1b
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spelling	oai:doaj.org-article:7eb1b9d661c04ff89accb593ab8daa1b2021-11-18T07:34:51ZThe PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.1932-620310.1371/journal.pone.0027087https://doaj.org/article/7eb1b9d661c04ff89accb593ab8daa1b2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22087248/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC).<h4>Methods</h4>We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV)-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection.<h4>Results</h4>PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001) increased in alcoholic cirrhosis with (53.7%) and without HCC (36.2%) but was not different between healthy controls (22.9%) and patients with cirrhosis (25.3%; p = 0.545) and HCC (30.2%; p = 0.071) due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR) 16.8 versus healthy controls; 95% confidence interval (CI) 6.68-42.43, p<0.001). Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24-6.42; p = 0.013) as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50-11.52; p = 0.006).<h4>Conclusion</h4>The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that should be taken into account in future HCC prevention studies.Hans Dieter NischalkeCordula BergerCarolin LudaThomas BergTobias MüllerFrank GrünhageFrank LammertMartin CoenenBenjamin KrämerChristian KörnerNatascha VidovicJohannes OldenburgJacob NattermannTilman SauerbruchUlrich SpenglerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27087 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hans Dieter Nischalke Cordula Berger Carolin Luda Thomas Berg Tobias Müller Frank Grünhage Frank Lammert Martin Coenen Benjamin Krämer Christian Körner Natascha Vidovic Johannes Oldenburg Jacob Nattermann Tilman Sauerbruch Ulrich Spengler The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.
description	<h4>Background</h4>An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC).<h4>Methods</h4>We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV)-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection.<h4>Results</h4>PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001) increased in alcoholic cirrhosis with (53.7%) and without HCC (36.2%) but was not different between healthy controls (22.9%) and patients with cirrhosis (25.3%; p = 0.545) and HCC (30.2%; p = 0.071) due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR) 16.8 versus healthy controls; 95% confidence interval (CI) 6.68-42.43, p<0.001). Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24-6.42; p = 0.013) as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50-11.52; p = 0.006).<h4>Conclusion</h4>The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that should be taken into account in future HCC prevention studies.
format	article
author	Hans Dieter Nischalke Cordula Berger Carolin Luda Thomas Berg Tobias Müller Frank Grünhage Frank Lammert Martin Coenen Benjamin Krämer Christian Körner Natascha Vidovic Johannes Oldenburg Jacob Nattermann Tilman Sauerbruch Ulrich Spengler
author_facet	Hans Dieter Nischalke Cordula Berger Carolin Luda Thomas Berg Tobias Müller Frank Grünhage Frank Lammert Martin Coenen Benjamin Krämer Christian Körner Natascha Vidovic Johannes Oldenburg Jacob Nattermann Tilman Sauerbruch Ulrich Spengler
author_sort	Hans Dieter Nischalke
title	The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.
title_short	The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.
title_full	The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.
title_fullStr	The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.
title_full_unstemmed	The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.
title_sort	pnpla3 rs738409 148m/m genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis c cirrhosis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/7eb1b9d661c04ff89accb593ab8daa1b
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The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.

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