Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity.

OBJECTIVES

To comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children.

METHODS

Two hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for PNPLA3, TM6SF2, GCKR, and MBOAT7 gene variants. Percentage hepatic fat content (HFF%) was measured by nuclear magnetic resonance.

RESULTS

HFF% was positively related with BMI, HOMAIR, metabolic syndrome, ALT, AST, γGT, and albumin. Carriers of [G] allele in PNPLA3, [T] allele in GCKR and [T] allele in TM6SF2 genes had significantly higher hepatic fat content than wild-type carriers. HFF% was explained for 8.7% by metabolic and for 16.1% by genetic factors and, a model including age, gender, BMI, HOMAIR, PNPLA3, GCKR, and TM6SF2 variants was the best predictor of HFF%, explaining 24.8% of its variation (P < 0.001). A weighted-genetic risk score combining PNPLA3, GCKR, and TM6SF2 risk alleles was associated with almost eightfold higher risk of NAFLD.

CONCLUSIONS

Our data highlighted the predominant role of genetic factors in determining the amount of liver fat content in children with obesity.