Abstract
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.
Highlights
Celiac disease (CD) is an immune-mediated enteropathy triggered by exposure to gluten in genetically susceptible subjects [1]
hepatic steatosis (HS) was found on ultrasound in 136 patients (36.7%), in accordance with previously reported prevalence of HS in CD [10]; the remaining 234 (63.3%) did not show any sign of liver steatosis
Our data from the genotyping assay for the analysis of PNPLA3 I148M variants revealed that the CC genotype was present in 194 subjects (52.4%), the CG genotype in 138 subjects (37.3%), and the GG genotype in 38 subjects (10.2%)
Summary
Celiac disease (CD) is an immune-mediated enteropathy triggered by exposure to gluten in genetically susceptible subjects [1]. Recent evidence has shown that weight modifications are frequent in patients with CD once they start following a gluten-free diet (GFD) [2,3], data about. Nutrients 2018, 10, 1239 this topic are still contradictory [4,5,6,7] These changes are often associated with the development of hypertension, dyslipidemia, diabetes mellitus, hepatic steatosis (HS), and metabolic syndrome (MS) [8,9]. The increase in weight and the subsequent development of HS and MS in CD could be due to the improvement in intestinal absorption (caused by the exclusion of gluten from the diet) in patients who are in a compensative hyperphagic state [10]. Many gluten-free foods are characterized by a glycemic index that is higher than that of equivalent gluten-containing foods [10]
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