PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence
Background and aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non‐alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrh...
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| Veröffentlicht in: | Liver international 2011-09, Vol.31 (8), p.1137-1143 |
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| creator | Falleti, Edmondo Fabris, Carlo Cmet, Sara Cussigh, Annarosa Bitetto, Davide Fontanini, Elisabetta Fornasiere, Ezio Bignulin, Sara Fumolo, Elisa Bignulin, Eleonora Pirisi, Mario Toniutto, Pierluigi |
| description | Background and aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non‐alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown.
Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end‐stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism‐based assay.
Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P |
| doi_str_mv | 10.1111/j.1478-3231.2011.02534.x |
| format | Article |
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Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end‐stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism‐based assay.
Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over‐represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06–2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/* carriers), to 97/295 (32.9%; male C/*carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001).
Conclusions: The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.</description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/j.1478-3231.2011.02534.x</identifier><identifier>PMID: 21745286</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular - enzymology ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - virology ; Case-Control Studies ; Chi-Square Distribution ; cirrhosis ; Fatty Liver - complications ; Female ; gender ; Gene Frequency ; genetic polymorphisms ; Genetic Predisposition to Disease ; Hepatitis B - complications ; Hepatitis C - complications ; hepatocellular carcinoma ; Heterozygote ; Homozygote ; Humans ; Italy ; Lipase - genetics ; Liver Cirrhosis - enzymology ; Liver Cirrhosis - genetics ; Liver Cirrhosis - virology ; Liver Cirrhosis, Alcoholic - enzymology ; Liver Cirrhosis, Alcoholic - genetics ; Liver Cirrhosis, Alcoholic - virology ; Liver Neoplasms - enzymology ; Liver Neoplasms - genetics ; Liver Neoplasms - virology ; Logistic Models ; Male ; Membrane Proteins - genetics ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; Odds Ratio ; PNPLA3 ; Polymorphism, Single Nucleotide ; Prognosis ; Risk Assessment ; Risk Factors ; Young Adult</subject><ispartof>Liver international, 2011-09, Vol.31 (8), p.1137-1143</ispartof><rights>2011 John Wiley & Sons A/S</rights><rights>2011 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4764-eac42ef8730809dc228a32cff4d3e0a6d760ec7730614441dcef02a8d25366173</citedby><cites>FETCH-LOGICAL-c4764-eac42ef8730809dc228a32cff4d3e0a6d760ec7730614441dcef02a8d25366173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1478-3231.2011.02534.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1478-3231.2011.02534.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21745286$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Falleti, Edmondo</creatorcontrib><creatorcontrib>Fabris, Carlo</creatorcontrib><creatorcontrib>Cmet, Sara</creatorcontrib><creatorcontrib>Cussigh, Annarosa</creatorcontrib><creatorcontrib>Bitetto, Davide</creatorcontrib><creatorcontrib>Fontanini, Elisabetta</creatorcontrib><creatorcontrib>Fornasiere, Ezio</creatorcontrib><creatorcontrib>Bignulin, Sara</creatorcontrib><creatorcontrib>Fumolo, Elisa</creatorcontrib><creatorcontrib>Bignulin, Eleonora</creatorcontrib><creatorcontrib>Pirisi, Mario</creatorcontrib><creatorcontrib>Toniutto, Pierluigi</creatorcontrib><title>PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence</title><title>Liver international</title><addtitle>Liver Int</addtitle><description>Background and aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non‐alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown.
Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end‐stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism‐based assay.
Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over‐represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06–2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/* carriers), to 97/295 (32.9%; male C/*carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001).
Conclusions: The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Carcinoma, Hepatocellular - enzymology</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - virology</subject><subject>Case-Control Studies</subject><subject>Chi-Square Distribution</subject><subject>cirrhosis</subject><subject>Fatty Liver - complications</subject><subject>Female</subject><subject>gender</subject><subject>Gene Frequency</subject><subject>genetic polymorphisms</subject><subject>Genetic Predisposition to Disease</subject><subject>Hepatitis B - complications</subject><subject>Hepatitis C - complications</subject><subject>hepatocellular carcinoma</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Italy</subject><subject>Lipase - genetics</subject><subject>Liver Cirrhosis - enzymology</subject><subject>Liver Cirrhosis - genetics</subject><subject>Liver Cirrhosis - virology</subject><subject>Liver Cirrhosis, Alcoholic - enzymology</subject><subject>Liver Cirrhosis, Alcoholic - genetics</subject><subject>Liver Cirrhosis, Alcoholic - virology</subject><subject>Liver Neoplasms - enzymology</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - virology</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>Middle Aged</subject><subject>Non-alcoholic Fatty Liver Disease</subject><subject>Odds Ratio</subject><subject>PNPLA3</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prognosis</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Young Adult</subject><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU1v1DAQtRCIlsJfQL5xSuqvxAkSh2oFS6VQisTH0TLOhHhx4tRO6O4f4HfjsGXPzGVGfu_NWO8hhCnJaarLXU6FrDLOOM0ZoTQnrOAi3z9C5yfg8Wlm_Aw9i3FHCK3rgj5FZ4xKUbCqPEe_b29umyuOQ5S8EqTeXG7x5N1h8GHqbRywHbGxIfQ-2vgaB3B6tn6MvZ3wvZ17PPeANaQ3538csO-ws78g4NZG0DFBY4t7mPTsDTi3OB2w0cHY0Q8ae2OWEGA08Bw96bSL8OKhX6Av795-3rzPmo_b681VkxkhS5GBNoJBV0lOKlK3hrFKc2a6TrQciC5bWRIwMsElFULQ1kBHmK7aZE9ZUskv0Kvj3in4uwXirAYb15_pEfwSVU2KUlackMSsjkwTfIwBOjUFO-hwUJSoNQS1U6u_avVarSGovyGofZK-fDiyfB-gPQn_uZ4Ib46Ee-vg8N-LVXP9dZ2SPjvqbZxhf9Lr8FOVkstCfbvZqqb-RJsPkirO_wAnXKVT</recordid><startdate>201109</startdate><enddate>201109</enddate><creator>Falleti, Edmondo</creator><creator>Fabris, Carlo</creator><creator>Cmet, Sara</creator><creator>Cussigh, Annarosa</creator><creator>Bitetto, Davide</creator><creator>Fontanini, Elisabetta</creator><creator>Fornasiere, Ezio</creator><creator>Bignulin, Sara</creator><creator>Fumolo, Elisa</creator><creator>Bignulin, Eleonora</creator><creator>Pirisi, Mario</creator><creator>Toniutto, Pierluigi</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201109</creationdate><title>PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence</title><author>Falleti, Edmondo ; Fabris, Carlo ; Cmet, Sara ; Cussigh, Annarosa ; Bitetto, Davide ; Fontanini, Elisabetta ; Fornasiere, Ezio ; Bignulin, Sara ; Fumolo, Elisa ; Bignulin, Eleonora ; Pirisi, Mario ; Toniutto, Pierluigi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4764-eac42ef8730809dc228a32cff4d3e0a6d760ec7730614441dcef02a8d25366173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Carcinoma, Hepatocellular - enzymology</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - virology</topic><topic>Case-Control Studies</topic><topic>Chi-Square Distribution</topic><topic>cirrhosis</topic><topic>Fatty Liver - complications</topic><topic>Female</topic><topic>gender</topic><topic>Gene Frequency</topic><topic>genetic polymorphisms</topic><topic>Genetic Predisposition to Disease</topic><topic>Hepatitis B - complications</topic><topic>Hepatitis C - complications</topic><topic>hepatocellular carcinoma</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Italy</topic><topic>Lipase - genetics</topic><topic>Liver Cirrhosis - enzymology</topic><topic>Liver Cirrhosis - genetics</topic><topic>Liver Cirrhosis - virology</topic><topic>Liver Cirrhosis, Alcoholic - enzymology</topic><topic>Liver Cirrhosis, Alcoholic - genetics</topic><topic>Liver Cirrhosis, Alcoholic - virology</topic><topic>Liver Neoplasms - enzymology</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - virology</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>Middle Aged</topic><topic>Non-alcoholic Fatty Liver Disease</topic><topic>Odds Ratio</topic><topic>PNPLA3</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prognosis</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Falleti, Edmondo</creatorcontrib><creatorcontrib>Fabris, Carlo</creatorcontrib><creatorcontrib>Cmet, Sara</creatorcontrib><creatorcontrib>Cussigh, Annarosa</creatorcontrib><creatorcontrib>Bitetto, Davide</creatorcontrib><creatorcontrib>Fontanini, Elisabetta</creatorcontrib><creatorcontrib>Fornasiere, Ezio</creatorcontrib><creatorcontrib>Bignulin, Sara</creatorcontrib><creatorcontrib>Fumolo, Elisa</creatorcontrib><creatorcontrib>Bignulin, Eleonora</creatorcontrib><creatorcontrib>Pirisi, Mario</creatorcontrib><creatorcontrib>Toniutto, Pierluigi</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Falleti, Edmondo</au><au>Fabris, Carlo</au><au>Cmet, Sara</au><au>Cussigh, Annarosa</au><au>Bitetto, Davide</au><au>Fontanini, Elisabetta</au><au>Fornasiere, Ezio</au><au>Bignulin, Sara</au><au>Fumolo, Elisa</au><au>Bignulin, Eleonora</au><au>Pirisi, Mario</au><au>Toniutto, Pierluigi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence</atitle><jtitle>Liver international</jtitle><addtitle>Liver Int</addtitle><date>2011-09</date><risdate>2011</risdate><volume>31</volume><issue>8</issue><spage>1137</spage><epage>1143</epage><pages>1137-1143</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><abstract>Background and aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non‐alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown.
Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end‐stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism‐based assay.
Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over‐represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06–2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/* carriers), to 97/295 (32.9%; male C/*carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001).
Conclusions: The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21745286</pmid><doi>10.1111/j.1478-3231.2011.02534.x</doi><tpages>7</tpages></addata></record> |
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| ispartof | Liver international, 2011-09, Vol.31 (8), p.1137-1143 |
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| subjects | Adult Aged Aged, 80 and over Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - virology Case-Control Studies Chi-Square Distribution cirrhosis Fatty Liver - complications Female gender Gene Frequency genetic polymorphisms Genetic Predisposition to Disease Hepatitis B - complications Hepatitis C - complications hepatocellular carcinoma Heterozygote Homozygote Humans Italy Lipase - genetics Liver Cirrhosis - enzymology Liver Cirrhosis - genetics Liver Cirrhosis - virology Liver Cirrhosis, Alcoholic - enzymology Liver Cirrhosis, Alcoholic - genetics Liver Cirrhosis, Alcoholic - virology Liver Neoplasms - enzymology Liver Neoplasms - genetics Liver Neoplasms - virology Logistic Models Male Membrane Proteins - genetics Middle Aged Non-alcoholic Fatty Liver Disease Odds Ratio PNPLA3 Polymorphism, Single Nucleotide Prognosis Risk Assessment Risk Factors Young Adult |
| title | PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence |
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