The dietary monounsaturated to saturated fatty acid ratio modulates the genetic effects of GCKR on serum lipid levels in children.

Background: Glucokinase regulator (GCKR) plays important roles in the regulation of glucokinase (GK) activity and the metabolism of glucose and lipids. We investigated whether the association between GCKR genetic variants with serum lipids in Korean adults is replicated in children, and whether these genetic influences might be modulated by dietary monounsaturated fatty acid relative to saturated fatty acid (MUFA:SFA) ratio.

Methods: We genotyped 711 children for GCKR variants, used 7495 adults in KARE database, and analyzed anthropometric, biochemical, and dietary measurements.

Results: The major allele carriers of rs780094 and rs780092 in adults had significantly higher serum total cholesterol and triglycerides levels compared to noncarriers. Five variants in children, including rs780094 and rs780092, correlated similarly with high total and low-density lipoprotein (LDL) cholesterol. When the dietary MUFA:SFA ratio was dichotomized (MUFA:SFA≥1 or <1), the aggravating effects of the major allele on total cholesterol, LDL cholesterol, and triglycerides were only evident in the group in which MUFA:SFA ratio was <1. Additionally, we observed that the GCKR haplotype with a functional variant, rs1260326, influenced lower total and LDL cholesterol in children whose MUFA:SFA ratio was <1.

Conclusion: We replicated the genetic association effect of GCKR on total cholesterol in children, and found that the interaction effects between GCKR genetic variants and the dietary MUFA:SFA ratio on lipid levels, were commonly observed in Korean adults and children.