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https://hdl.handle.net/2440/82529
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dc.contributor.author | Dongiovanni, P. | - |
dc.contributor.author | Valenti, L. | - |
dc.contributor.author | Rametta, R. | - |
dc.contributor.author | Daly, A. | - |
dc.contributor.author | Nobili, V. | - |
dc.contributor.author | Mozzi, E. | - |
dc.contributor.author | Leathart, J. | - |
dc.contributor.author | Pietrobattista, A. | - |
dc.contributor.author | Burt, A. | - |
dc.contributor.author | Maggioni, M. | - |
dc.contributor.author | Fracanzani, A. | - |
dc.contributor.author | Lattuada, E. | - |
dc.contributor.author | Zappa, M. | - |
dc.contributor.author | Roviaro, G. | - |
dc.contributor.author | Marchesini, G. | - |
dc.contributor.author | Day, C. | - |
dc.contributor.author | Fargion, S. | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | Gut, 2010; 59(2):267-273 | - |
dc.identifier.issn | 0017-5749 | - |
dc.identifier.issn | 1468-3288 | - |
dc.identifier.uri | http://hdl.handle.net/2440/82529 | - |
dc.description.abstract | BACKGROUND/AIMS The aim of this study was to assess the effect of functional ENPP1(ectoenzyme nucleotide pyrophosphate phosphodiesterase 1)/PC-1 (plasma cell antigen-1) and IRS-1 (insulin receptor substrate-1) polymorphisms influencing insulin receptor activity on liver damage in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, whose progression is associated with the severity of insulin resistance. PATIENTS AND METHODS 702 patients with biopsy-proven NAFLD from Italy and the UK, and 310 healthy controls. The Lys121Gln ENPP1/PC-1 and the Gly972Arg IRS-1 polymorphisms were evaluated by restriction analysis. Fibrosis was evaluated according to Kleiner. Insulin signalling activity was evaluated by measuring phosphoAKT levels by western blotting in a subset of obese non-diabetic patients. RESULTS The ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively. The ENPP1 121Gln allele was significantly associated with increased prevalence of fibrosis stage >1 and >2, which was higher in subjects also positive for the 972Arg IRS-1 polymorphism. At multivariate analysis, the presence of the ENPP1 121Gln and IRS-1 972Arg polymorphisms was independently associated with fibrosis >1 (OR 1.55, 95% CI 1.24 to 1.97; and OR 1.57, 95% CI 1.12 to 2.23, respectively). Both polymorphisms were associated with a marked reduction of ∼70% of AKT activation status, reflecting insulin resistance and disease severity, in obese patients with NAFLD. CONCLUSIONS The ENPP1 121Gln and IRS-1 972Arg polymorphisms affecting insulin receptor activity predispose to liver damage and decrease hepatic insulin signalling in patients with NAFLD. Defective insulin signalling may play a causal role in the progression of liver damage in NAFLD. | - |
dc.description.statementofresponsibility | P Dongiovanni, L Valenti, R Rametta, A K Daly, V Nobili, E Mozzi, J B S Leathart, A Pietrobattista, A D Burt, M Maggioni, A L Fracanzani, E Lattuada, M A Zappa, G Roviaro, G Marchesini, C P Day, S Fargion | - |
dc.language.iso | en | - |
dc.publisher | British Med Journal Publ Group | - |
dc.rights | Copyright status unknown | - |
dc.source.uri | http://gut.bmj.com/content/59/2/267 | - |
dc.subject | Humans | - |
dc.subject | Fatty Liver | - |
dc.subject | Insulin Resistance | - |
dc.subject | Genetic Predisposition to Disease | - |
dc.subject | Pyrophosphatases | - |
dc.subject | Phosphoric Diester Hydrolases | - |
dc.subject | Receptor, Insulin | - |
dc.subject | Severity of Illness Index | - |
dc.subject | Signal Transduction | - |
dc.subject | Polymorphism, Single Nucleotide | - |
dc.subject | Adult | - |
dc.subject | Middle Aged | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.subject | Insulin Receptor Substrate Proteins | - |
dc.title | Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1136/gut.2009.190801 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Burt, A. [0000-0002-3011-7774] | - |
Appears in Collections: | Aurora harvest Medicine publications |
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