Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents.
Level 4 - case-series / case-control
Cross-sectional genetic association study
PubMed 22105854 · doi:10.1002/hep.24806
What was done
The authors investigated whether the glucokinase regulatory protein (GCKR) gene variant rs1260326 is associated with hepatic fat content (HFF%) and plasma lipids, alone and in combination with PNPLA3 (rs738409) and APOC3 (rs2854116) variants. They studied 455 obese children and adolescents (181 Caucasians, 139 African Americans, and 135 Hispanics). All participants underwent an oral glucose tolerance test and fasting lipoprotein subclass measurement by proton nuclear magnetic resonance. A subset of 142 children underwent fast gradient magnetic resonance imaging to measure HFF%.
What was found
The GCKR rs1260326 variant was associated with elevated triglycerides in Caucasians (P = 0.00014) and African Americans (P = 0.00417), large VLDL in Caucasians (P = 0.001) and African Americans (P = 0.03), and fatty liver in Caucasians (P = 0.034), African Americans (P = 0.00002), and Hispanics (P = 0.016). PNPLA3, but not APOC3 rs2854116, was associated with fatty liver but not with triglyceride levels. The joint effect between PNPLA3 and GCKR SNPs explained 32% of HFF% variance in Caucasians (P = 0.00161), 39.0% in African Americans (P = 0.00000496), and 15% in Hispanics (P = 0.00342).
Why it matters
The study shows that GCKR rs1260326 is linked to dyslipidemia and hepatic steatosis in pediatric obesity, acting jointly with PNPLA3 to explain a substantial proportion of hepatic fat fraction variance across multiple ethnic groups.
Limits
The study is cross-sectional, precluding longitudinal or causal inference. Direct quantification of hepatic fat fraction by MRI was restricted to a subset of 142 participants out of 455. Specific effect sizes, odds ratios, and confidence intervals are not reported in the abstract.
Cited by
- contradicts African Americans accumulate less hepatic fat on average due to a mutation in the APOC3 gene.