Genetic and Clinical Markers of Elevated Liver Fat Content in Overweight and Obese Hispanic Children

OBJECTIVE: Genetic variation in six genes has been associated with elevated liver fat and nonalcoholic fatty liver disease in adults. We sought to determine the influence of these genes on liver fat and whether a genetic risk score (GRS) would improve upon the ability of common clinical risk factors to predict elevated liver fat content (ELF) in Hispanic children. DESIGN AND METHODS: 223 obese Hispanic children were genotyped for six SNPs. MRI was used to measure liver fat. A GRS was tested for association with ELF using multivariate linear regression. Predictors were assessed via ROC curves and pair-wise analysis was used to determine significance alone and combined with clinical markers. RESULTS: Only variants in PNPLA3 and APOC3 genes were associated with liver fat (p<0.001, p=0.01, respectively). Subjects with a GRS=4 had ~3-fold higher liver fat content than subjects with GRS of 0 (15.1±12.7% vs. 5.1±3.7%, p=0.03). While the addition of the GRS to a model containing BMI and liver enzymes increased ROC AUC from 0.83 to 0.85 [95% CI, 0.79-0.89], (p=0.01), it does not improve detection of ELF from a clinical perspective. CONCLUSIONS: Only PNPLA3 and APOC3 were related to ELF and a GRS comprised of these susceptibility alleles did not add to the discriminatory power of traditional biomarkers for clinical assessment of liver fat.