Glucokinase Regulatory Protein Gene Polymorphism Affects Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Luca Miele, Stefania Boccia, Antonio Grieco, Salvatore Petta, Elisabetta Bugianesi, Calogero Cammà, Chiara Rosso, Daniela Cabibi, Vito Di Marco, Stefania Grimaudo, Rosaria Maria Pipitone, Giulio Marchesini, Antonio Craxì

Risultato della ricerca: Contributo in rivistaArticolo in rivista

77 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaPLoS One
Volume9
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

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

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