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PNPLA3 rs738409 Polymorphism Predicts Development and Severity of Hepatic Steatosis but Not Metabolic Syndrome in Celiac Disease

Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine “Federico II” of Naples, Via S. Pansini 5, 80131 Naples, Italy
Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children’s Hospital-IRCCS, 00165 Rome, Italy
Ferretti: 1. Hepatology, Gastroenterology and Nutrition, “Bambino Gesù” Children’s Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy
Pediatric Department, University La Sapienza Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Department of Internal Medicine and Gastroenterology, Catholic University, 00128 Rome, Italy
Author to whom correspondence should be addressed.
Nutrients 2018, 10(9), 1239;
Received: 20 August 2018 / Revised: 30 August 2018 / Accepted: 4 September 2018 / Published: 5 September 2018
Metabolic syndrome (MS) and hepatic steatosis (HS) have been described in patients with celiac disease (CD) after starting a gluten-free diet (GFD), but data on predictive factors for these conditions are scarce. Recently, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 has been identified as a key factor for HS development in the general population. The aim of the study was to evaluate the role of PNPLA3 rs738409 in the development of MS and HS in CD patients after starting GFD. Between June 2014 and September 2016, we consecutively enrolled CD patients with HS, while those without steatosis served as a control group. All patients underwent anthropometric and serologic investigations, ultrasonography (US) to assess the degree and severity of HS, and genotyping of the PNPLA3 rs738409 polymorphism. Finally, 370 subjects were enrolled (136 with and 234 without HS). At genotyping assays, the CC genotype was found in 194 subjects (52.4%), the CG genotype in 138 subjects (37.3%), and the GG genotype in 38 subjects (10.2%). At binary logistic regression, only CG and GG alleles were predictive for the development of HS (odds ratio (OR) 1.97; p < 0.01 for CG and OR 6.9; p < 0.001 for GG). Body mass index (BMI) (OR 3.8; p < 0.001) and waist circumference (OR 2.8; p = 0.03) at CD diagnosis were the only independent factors for the development of MS. Intergroup comparisons showed that the severe grade of HS was more frequently observed in GG than in CC carriers (74% vs. 11.3%, p < 0.001, OR 21.8). PNPLA3 CG and GG carriers with CD have a higher susceptibility to hepatic steatosis, but not to metabolic syndrome. Moreover, patients with GG alleles display more severe forms of HS based on ultrasound. View Full-Text
Keywords: celiac disease; metabolic syndrome; hepatic steatosis; PNPLA3 celiac disease; metabolic syndrome; hepatic steatosis; PNPLA3
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Tortora, R.; Rispo, A.; Alisi, A.; Imperatore, N.; Crudele, A.; Ferretti, F.; Nobili, V.; Miele, L.; Gerbino, N.; Caporaso, N.; Morisco, F. PNPLA3 rs738409 Polymorphism Predicts Development and Severity of Hepatic Steatosis but Not Metabolic Syndrome in Celiac Disease. Nutrients 2018, 10, 1239.

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