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Jean-Michel Petit, Boris Guiu, David Masson, Laurence Duvillard, Valerie Jooste, Perrine Buffier, Beatrice Terriat, Benjamin Bouillet, Marie-Claude Brindisi, Romaric Loffroy, Isabelle Robin, Patrick Hillon, Jean-Pierre Cercueil, Bruno Verges, Specifically PNPLA3-Mediated Accumulation of Liver Fat in Obese Patients with Type 2 Diabetes, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 12, 1 December 2010, Pages E430–E436, https://doi.org/10.1210/jc.2010-0814
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Context: Recently, it has been shown in the general population that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC), independently of visceral adiposity and insulin resistance.
Objective: In this study, we set out to determine whether LFC, evaluated using 1H-MR spectroscopy, was associated with PNPLA3 rs738409 polymorphism in people with type 2 diabetes. We also evaluated the influence of this polymorphism on the relationship between LFC and either visceral adiposity or carotid intima media thickness (CIMT).
Design, Settings, and Participants: A total of 218 type 2 diabetic patients were included in this study.
Main Outcome Measures: LFC, area of visceral fat, and CIMT were measured.
Results: A total of 139 (63.7%) patients had steatosis. The rs738409 minor G allele was associated with LFC. The number of patients with steatosis was significantly higher among minor G allele carriers in comparison to C allele homozygote carriers (70.3 vs. 57.2%; P = 0.04) In the subgroup of C allele homozygote carriers, LFC correlated with body mass index (r = 0.27; P = 0.003) and visceral fat area (r = 0.30; P = 0.002), but not with CIMT. In the subgroup of minor G allele carriers, LFC correlated inversely with CIMT (r = −0.23; P = 0.03), but not with body mass index or with visceral fat area. In multivariate logistic regression, the relationship between the highest quartile of CIMT and steatosis was different according to adiponutrin polymorphism.
Conclusions: This study confirms that in people with type 2 diabetes, LFC is related to rs738409 polymorphism. The lack of a relationship with visceral obesity and the inverse correlation with CIMT suggest that fatty liver associated with the minor G allele of the PNPLA3 rs738409 polymorphism may not be linked to metabolic disorders.
