Genetic susceptibility of increased intestinal permeability is associated with progressive liver disease and diabetes in patients with non-alcoholic fatty liver disease.
Adult
Case-Control Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 2
/ diagnosis
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Intestinal Absorption
/ genetics
Italy
/ epidemiology
Liver Cirrhosis
/ epidemiology
Male
Middle Aged
Non-alcoholic Fatty Liver Disease
/ diagnosis
Permeability
Phenotype
Polymorphism, Single Nucleotide
Prevalence
Prospective Studies
Protein Tyrosine Phosphatase, Non-Receptor Type 2
/ genetics
Risk Assessment
Risk Factors
Severity of Illness Index
Genetic susceptibility
Intestinal permeability
Nonalcoholic fatty liver disease
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
30 10 2020
30 10 2020
Historique:
received:
21
04
2020
revised:
12
06
2020
accepted:
12
06
2020
pubmed:
19
8
2020
medline:
15
12
2020
entrez:
19
8
2020
Statut:
ppublish
Résumé
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). 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 32807638
pii: S0939-4753(20)30242-8
doi: 10.1016/j.numecd.2020.06.013
pii:
doi:
Substances chimiques
PTPN2 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 2
EC 3.1.3.48
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2103-2110Informations de copyright
Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no competing interest.