Genetic and clinical markers of elevated liver fat content in overweight and obese Hispanic children

Obesity (Silver Spring). 2013 Dec;21(12):E790-7. doi: 10.1002/oby.20523. Epub 2013 Aug 13.

Abstract

Objective: Genetic variation in six genes has been associated with elevated liver fat and nonalcoholic fatty liver disease in adults. 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 was determined.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alanine Transaminase / blood
  • Alleles
  • Anthropometry
  • Apolipoprotein C-III / genetics
  • Apolipoprotein C-III / metabolism
  • Aspartate Aminotransferases / blood
  • Blood Glucose / metabolism
  • Body Composition
  • Body Mass Index
  • Child
  • Cross-Sectional Studies
  • Fatty Liver / genetics*
  • Female
  • Genotype
  • Hispanic Americans / genetics*
  • Humans
  • Lipase / genetics
  • Lipase / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Non-alcoholic Fatty Liver Disease
  • Obesity / genetics*
  • Overweight / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Triglycerides / metabolism

Substances

  • Apolipoprotein C-III
  • Blood Glucose
  • Membrane Proteins
  • Triglycerides
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Lipase
  • adiponutrin, human