Impact of PNPLA3 rs738409 polymorphism on the development of liver-related events in patients with non-alcoholic fatty liver disease

Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a complex disease, resulting from the interplay between environmental determinants and genetic variations. Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene is associated with hepatic fibrosis and with higher risk of developing hepatocellular carcinoma. Here, we analysed a longitudinal cohort of biopsy-proven NAFLD subjects with the aim to identify individuals in whom genetics may have a stronger impact on disease progression. Methods: We retrospectively analyzed 756 consecutive, prospectively enrolled biopsy-proven NAFLD subjects from Italy, UK and Spain who were followed for a median of 84 months (interquartile range 65 - 109 months). We stratified the study cohort according to sex, body mass index (BMI)