Avocados are rich in unsaturated fat and dietary fiber, and recent clinical trials have investigated their effects on management of obesity and hypercholesterolemia. However, there is great response heterogeneity following avocado consumption. This variability may be due to genetic differences. The rs1260326 variant of glucokinase regulator (GCKR) has been previously associated with adiposity and metabolic dysfunction. However, the effects of this variant on hypercholesterolemia and response to dietary interventions are less understood.


Adults (n=115) ages 25-45 years with BMI ≥ 25 kg/m2 were randomized to receive a 12-week daily meal with or without avocado. The control meals were isocaloric, but higher in saturated fat and lower in fiber than intervention meals. Venous blood was collected at baseline and at 12-week follow-up to determine total cholesterol (TC) concentrations. Genomic DNA was extracted from blood and genotyped for GCKR-rs1260326.


There was no significant group-by-time effects detected for TC changes (P=0.96). However, there was a significant group-by-time-by-genotype interaction detected for GCKR-rs1260326 (P=0.01) associated with TC changes whereby C-homozygotes in the avocado group (n=20) experienced a significant decrease in TC by 9.3 (standard error [SE]: 3.5) mg/dL compared to the 3.2 (SE: 3.5) mg/dL increase observed in the T-allele carriers (P=0.02).


Genotype of GCKR-rs1260326 was associated with inverse response in TC following daily 12-week avocado consumption. Presence of the rs1260326 T allele results in decreased regulation of GCKR, leading to increased hepatic glucose uptake, lipogenesis, and hepatic triglyceride output. These findings indicate that daily consumption of avocado among C-homozygotes may be effective in managing hypercholesterolemia, but less effective among T-allele carriers. Genetic variation may play a role in determining response to dietary interventions, potentially informing personalized nutrition recommendations.