icon-folder.gif   Conference Reports for NATAP  
 
  EASL
42nd Meeting of the European Association for the Study of Liver Diseases
Barcelona, Spain
April 11-15, 2007
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Inherited Variants of Genes Involved in Insulin Signaling and Lipogenesis Influence The Risk of Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease
 
 
  EASL, April 2007, Barcelona, Spain
 
P. Dongiovanni 1, L. Valenti 1, R. Rametta 1, A.L. Fracanzani 1, S. Fargion 1 1 Department Of Internal Medicine, Universita Di Milano, Ospedale Policlinico IRCCS, Milano, Italy
 
Background & aims: Inherited factors play a major role in the pathogenesis of the metabolic syndrome, whose hepatic expression is NAFLD, a leading cause of liver disease. The study aim was to assess the role of well-characterized functional polymorphisms of genes involved in insulin signaling and lipogenesis on the risk of NAFLD progression to fibrosis.
 
Patients and Methods: 235 patients with NAFLD, 150 with liver biopsy (57 with and 93 without fibrosis), and 135 controls. The Leu162Val PPARalpha, Pro12Ala PPARgamma2, Lys121Gln PC-1, Gly972Arg IRS-1, and Glu84Arg TRB3 polymorphisms were determined by restriction analysis (see Table). Data were compared by chi-square and t-Test, when appropriate. The risk of fibrosis was adjusted by logistic regression analysis considering as independent variables genetic polymorphisms, age, ALT, and ferritin levels.
 
Results:
 
At univariate analysis, the IRS-1 972Arg and the PPARalpha 162Val alleles, previously linked to insulin resistance, were associated with higher prevalence of diabetes/impaired glucose tolerance and higher HOMA insulin resistance index (p<.05).
 
The IRS-1 972Arg allele (prevalence 13% in NAFLD) was associated with higher prevalence of fibrosis in biopsied patients (55% in positive patients vs. 36% in negative ones; OR 2.5, 95% CI 0.99-7; p=.06), whereas the gain of function 84Arg allele (prevalence 23% in NAFLD) of TRB3, which inhibits lipogenesis, was associated with lower fibrosis (28% in positive patients vs. 43% in negative ones; OR 0.39, 95% CI 0.15-0.95; p=.04).
 
Conclusions:
Genetic factors affecting lipogenesis and insulin signaling, which regulates metabolism and survival of hepatocytes, are associated with the progression of liver damage in NAFLD.

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