Genetic susceptibility of increased intestinal permeability is associated with progressive liver disease and diabetes in patients with non-alcoholic fatty liver disease

Luca Miele, Gian Ludovico Rapaccini, Stefania Boccia, Antonio Gasbarrini, Antonio Grieco, Valentina Giorgio, Antonio Liguori, Roberta Pastorino, Chiara Maria Assunta Cefalo, Giuseppe Marrone, Marco Biolato, Salvatore Petta, Dario Arzani, Consuelo Cefalo, Gianludovico Rapaccini, Antonio Craxì

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background and aim: Increased intestinal permeability plays a key role in the pathogenesis of fat deposition in the liver. The aim of our study was to assess whether a single nucleotide polymorphism of protein tyrosine phosphatase non-receptor type 2 (PTPN2) (rs2542151 T→G), involved in intestinal permeability, may be associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods and results: We recruited a prospective cohort of NAFLD subjects and matched controls. Clinical data, PTPN2 genotype and laboratory data were collected for each patient. Results were stratified according to liver histology and diabetes. We enrolled 566 cases and 377 controls. PTPN2 genotype distribution did not significantly differ between patients and controls. In the entire population, patients with PTPN2 rs2542151 T→G (dominant model) have a higher prevalence of diabetes; 345 patients (60.9%) underwent liver biopsy: 198 (57.4%) had steatohepatitis and 75 (21.7%) had advanced fibrosis. At multiple logistic regression analysis PTPN2 rs2542151 T→G was associated with T2DM (OR 2.14, 95% CI 1.04–4.40, P = 0.03). Patients who underwent liver biopsy, rs2542151 T→G of PTPN2 was independently associated with severe steatosis (OR 2.00, 95% CI 1.17–3.43, p = 0.01) and severe fibrosis (OR 2.23, 95% CI 1.06–4.72, P = 0.03). Conclusion: Our study shows that NAFLD patients with rs2542151 T→G of PTPN2 have a higher severity of fatty liver disease and a higher prevalence of T2DM. These results suggest that individual genetic susceptibility to intestinal permeability could play a role in liver disease progression.
Original languageEnglish
Pages (from-to)N/A-N/A
JournalNMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
DOIs
Publication statusPublished - 2020

Keywords

  • Genetic susceptibility
  • Intestinal permeability
  • Nonalcoholic fatty liver disease

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