The Frequent Adiponutrin (PNPLA3) Variant p.Ile148Met Is Associated with Early Liver Injury: Analysis of a German Pediatric Cohort

Abstract

Introduction. The common adiponutrin (PNPLA3) variant p.Ile148Met is associated with liver injury. Here, we investigate the association of this polymorphism with hepatic and metabolic traits in a pediatric cohort. Patients and Methods. The study cohort comprised 142 German children (age 5–9 years, 98 overweight, 19 children with NAFLD). Results. Overweight children presented with increased serum ALT (P=0.001) and GGT (P<0.001) activities. ALT activities differed significantly (P=0.02) between carriers of different PNPLA3 genotypes in the entire study cohort, in normal weight children (P=0.02) and in children younger than 7 years (P=0.02). Carriers of the prosteatotic PNPLA3 genotype p.148Met/Met displayed higher ALT activities as compared to children with the frequent genotype p.148Ile/Ile (P=0.01). The BMI was however a stronger predictor of ALT activities compared to the PNPLA3 genotype (P<0.001 and P=0.06, resp.). The variant was associated with increased serum glucose levels (P=0.01) and HOMA index (P=0.02) in carriers of the p.148Ile/Met genotype but did not affect other metabolic traits or the presence of NAFLD. Discussion. The frequent PNPLA3 variant p.Ile148Met is associated with serum ALT activities already at a young age.