The frequent PNPLA3 risk variant p.I148 M is associated with decreased pruritus in cholestasis: novel role of a prosteatotic polymorphism

Background and aims: The common PNPLA3 (adiponutrin) variant p.I148 M is associated with severe forms of liver diseases1. Of note, the minor allele [M] at this locus promotes the conversion of lysophosphatidic acid (LPA) into phosphatidic acid (PA)2, resulting in increased cellular diacylglycerol synthesis. Since LPA functions as a mediator of cholestatic pruritus3, we now investigate the effects of the PNPLA3 variant on itching in patients with primary biliary cirrhosis (PBC) and intrahepatic cholestasis of pregnancy (ICP). Methods: We recruited 186 PBC patients (age range 22 – 83 years, 165 females, 68 with li…