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

Marcin Krawczyk,Frank Lammert,Anna Janina Engstler,Ina B Maier,Roman Liebe,Ina Bergheim

doi:10.1155/2015/205079

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.

Highlights

The common adiponutrin (PNPLA3) variant p.Ile148Met is associated with liver injury
In the whole cohort we observed the following genotype frequencies: patatin-like phospholipase domain containing gene 3 (PNPLA3) p.148Ile/Ile = 75 (52.8%), PNPLA3 p.148Ile/Met = 57 (40.1%), and PNPLA3 p.148Met/Met = 10 (7.1%). These frequencies did not differ significantly from values presented in previous publications [14] and were in line with Hardy-Weinberg equilibrium (HWE) (P = 0.99)
There was no association between the PNPLA3 genotype and presence of fatty liver as assessed by abdominal sonography (N = 19, P > 0.05)

Summary

Introduction

The common adiponutrin (PNPLA3) variant p.Ile148Met is associated with liver injury. 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 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. The frequent PNPLA3 variant p.Ile148Met is associated with serum ALT activities already at a young age. As in many countries like Germany, assessment of liver status is not mandatory in children and adolescents and most available data to date were derived in clinical setting, the real figure may be even higher

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Results

Discussion

Conclusion