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

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.

SUBMITTER: Petta S 

PROVIDER: S-EPMC3911959 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature