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

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.

Celiac Disease, Gluten-Free Diet, and Metabolic and Liver Disorders

“…Moreover, an overall increase in BMI after starting a GFD was observed in three other studies (Table 1) [31][32][33].…”

“…Nine studies assessed the BMI changes in CD patients before and after starting a GFD [4,11,[29][30][31][32][33][34][35]. Six of these studies analyzed BMI changes as expressed by the mean or median (Table 1)…”

“…Nine studies assessed the BMI changes in CD patients before and after starting a GFD [4,11,[29][30][31][32][33][34][35]. Six of these studies analyzed BMI changes as expressed by the mean or median (Table 1) [11,[29][30][31][32][33], while the remaining three studies evaluated the number of patients with changes in their BMIs in terms of a percentage [4,34,35].…”

“…There were three studies found that assessed lipid levels before and after the initiation of a GFD (Table 2) [32,33,35] and one study that reported the prevalence of dyslipidemia in celiac patients on a GFD [22]. In a case-control study, increasing triglyceride blood levels were observed after the diagnosis of CD in patients following a GFD at a follow-up of 4.7 years [33]. In another prospective study, however, the same authors did not find significant changes in the levels of triglycerides (although this was only after a one-year follow-up) [32].…”

“…There were two studies found that assessed the prevalence of T2DM in CD patients on a GFD (Table 3) [22,36], and two studies examined the glycemia level before and after the start of a GFD [32,33]. In a cross-sectional study involving 840 CD patients and 840 healthy subjects, the prevalence of T2DM was three times lower in the celiac group than in the matched control and in the general population [22].…”