The PNPLA3 I148M variant and chronic liver disease: When a genetic mutation meets nutrients

•The PNPLA3 I148M variant is associated with chronic liver disease.•Nutrients interact with the PNPLA3 variant in determining liver disease.•Studying the interplay between variants and nutrients is an example of nutrigenetics.

The isoleucine to methionine substitution at position 148 in the patatin-like phospholipase domain containing 3 protein (PNPLA3; I148M variant, rs738409) is associated with liver fat accumulation and an increased risk of chronic liver disease ranging from hepatitis to hepatocellular carcinoma. This review discusses the interaction between the PNPLA3 I148M variant and obesity/intake of specific nutrients in determining the susceptibility to liver disease. We present the results of several studies showing that obesity or alcohol abuse enhances the effect of the PNPLA3 I148M variant on the liver. We also show that specific nutrients interact with the PNPLA3 I148M variant in modulating liver disease susceptibility.