Histological hepatocyte damage precedes steatosis in ALD patients with genetic variant l148 M in PNPLA3

Aim: The non-synonymous single nucleotide polymorphism rs738409C->G in PNPLA3 that substitutes methionine for isoleucine at residue 148 (I148 M) has been identified as major genetic confounding factor of liver steatosis and fibrosis progression both in patients with alcoholic and non-alcoholic liver disease (ALD and NAFLD). Since the PNPLA3 function remains largely unknown, we here studied in detail sub-histological scores and mRNA transcripts in a large cohort of well characterized ALD patients. Patients and methods: 217 patients with ALD were enrolled for PNPLA3 genotype analysis (RT-PCR) with routine laborato…