PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes

• Published in: Liver international Vol. 31; no. 9; pp. 1332 - 1336
• Main Authors: Petit, Jean M., Guiu, Boris, Masson, David, Duvillard, Laurence, Jooste, Valerie, Buffier, Perrine, Bouillet, Benjamin, Brindisi, Marie-Claude, Robin, Isabelle, Gambert, Philippe, Verges, Bruno, Cercueil, Jean-Pierre, Hillon, Patrick
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2011
• Subjects: 1H-spectroscopy; adiponutrin; Aged; Biomarkers - blood; Body Mass Index; Chi-Square Distribution; Cross-Sectional Studies; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - genetics; Fatty Liver - enzymology; Fatty Liver - genetics; Female; FibroTest; France; Gene Frequency; Genetic Predisposition to Disease; Homozygote; Humans; Lipase - genetics; Liver - enzymology; Liver - pathology; Liver Cirrhosis - blood; Liver Cirrhosis - enzymology; Liver Cirrhosis - genetics; Liver Cirrhosis - pathology; liver fibrosis; Logistic Models; Magnetic Resonance Spectroscopy; Male; Membrane Proteins - genetics; Middle Aged; Non-alcoholic Fatty Liver Disease; Odds Ratio; Phenotype; Polymorphism, Genetic; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; steatosis; type 2 diabetes; France
• ISSN: 1478-3223; 1478-3231; 1478-3231
• DOI: 10.1111/j.1478-3231.2011.02566.x

Context: Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance. Objective: In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in unselected patients with type 2 diabetes. Design, setting and participants: Two hundred and thirty‐four patients with type 2 diabetes were included in this study. Main outcome measures: LFC was evaluated using 1H‐MR spectroscopy; fibrosis was measured using the non‐invasive FibroTest®. Results: Advanced liver fibrosis (stage F2 or above) was observed in 10.2% of the patients while 149 (63.6%) patients had steatosis. The prevalence of steatosis and fibrosis was higher in minor G allele carriers than that in C allele homozygote carriers (70.3 vs 57.1%; P=0.04 and 14.7 vs 7.5%; P=0.07 respectively). In multivariate analysis, the predictive variables for advanced liver fibrosis were age (≥60) (P=0.005), sex (female) (P=0.004) and rs 738409 PNPLA3 polymorphism (P=0.01); body mass index (BMI) and LFC were not associated with liver fibrosis. Conclusions: This study confirms that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fibrosis was related to the rs738409 polymorphism independent of BMI or LFC.