PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes

Context: Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance. Objective: In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in un-selected patients with type 2 diabetes. Design, setting and participants: Two hundred and thirty-four patients with type 2 diabetes were included in this study. Main outcome measures: LFC was evaluated using H-1-MR spectroscopy; fibrosis was measured using the non-invasive FibroTest (R). Results: Advanced liver fibrosis (stage F2 or above) was observed in 10.2% of the patients while 149 (63.6%) patients had steatosis. The prevalence of steatosis and fibrosis was higher in minor G allele carriers than that in C allele homozygote carriers (70.3 vs 57.1%; P=0.04 and 14.7 vs 7.5%; P=0.07 respectively). In multivariate analysis, the predictive variables for advanced liver fibrosis were age (>= 60) (P=0.005), sex (female) (P=0.004) and rs 738409 PNPLA3 polymorphism (P=0.01); body mass index (BMI) and LFC were not associated with liver fibrosis. Conclusions: This study confirms that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fibrosis was related to the rs738409 polymorphism independent of BMI or LFC.