Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease

PLoS One. 2014 Feb 3;9(2):e87523. doi: 10.1371/journal.pone.0087523. eCollection 2014.

Abstract

Background and aims: Variant in glucokinase regulatory protein (GCKR), associated with lipid and glucose traits, has been suggested to affect fatty liver infiltration. We aimed to assess whether GCKR rs780094 C→T SNP influences the expression of steatosis, lobular inflammation and fibrosis in NAFLD patients, after correction for PNPLA3 genotype.

Methods: In 366 consecutive NAFLD patients (197 from Sicily, and 169 from center/northern Italy), we assessed anthropometric, biochemical and metabolic features; liver biopsy was scored according to Kleiner. PNPLA3 rs738409 C>G and GCKR rs780094 C>T single nucleotide polymorphisms were also assessed.

Results: At multivariate logistic regression analysis in the entire NAFLD cohort, the presence of significant liver fibrosis (>F1) was independently linked to high HOMA (OR 1.12, 95% CI 1.01-1.23, p = 0.02), NAFLD activity score ≥ 5 (OR 4.09, 95% CI 2.45-6.81, p<0.001), and GCKR C>T SNP (OR 2.06, 95% CI 1.43-2.98, p<0.001). Similar results were observed considering separately the two different NAFLD cohorts. GCKR C>T SNP was also associated with higher serum triglycerides (ANOVA, p = 0.02) in the entire cohort.

Conclusions: In patients with NAFLD, GCKR rs780094 C>T is associated with the severity of liver fibrosis and with higher serum triglyceride levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Italy
  • Lipase / genetics
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / metabolism
  • Logistic Models
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Multivariate Analysis
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Sicily
  • Triglycerides / blood

Substances

  • Adaptor Proteins, Signal Transducing
  • GCKR protein, human
  • Membrane Proteins
  • Triglycerides
  • Lipase
  • adiponutrin, human

Grants and funding

This study was funded by grants from the FP7/2007–2013 (n°Health-F2-2009-241762), from PRIN 2009 (Prot. N. 2009ARYX4T_004), and from PRIN 2010–2011 (Prot. N. 2010C4JJWB_001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.