Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease

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

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Pages (from-to)267-273
Number of pages7
JournalGut
Volume59
Issue number2
DOIs
Publication statusPublished - Feb 2010

ASJC Scopus subject areas

  • Gastroenterology

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