APOA5 genotype modulates 2-y changes in lipid profile in response to weight-loss diet intervention: the Pounds Lost Trial

Abstract

Background: The apolipoprotein A5 gene (APOA5) is a major gene that regulates lipid metabolism and is modulated by dietary factors. A novel variant rs964184 in APOA5 was identified to be associated with lipids in genome-wide association studies.

Objective: We examined whether this variant modified changes in lipid concentrations in response to a 2-y weight-loss diet intervention in a randomized trial.

Design: The current analyses were secondary analyses of a data set from the Pounds Lost Trial. We genotyped APOA5 rs964184 in 734 overweight or obese adults who were randomly assigned to one of 4 diets that differed in percentages of energy derived from fat, protein, and carbohydrate for 2 y. We evaluated changes in fasting serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglyceride from baseline to 2 y of follow-up.

Results: After a 2-y dietary intervention, we showed significant interactions between the APOA5 rs964184 polymorphism and dietary fat intake (low compared with high) in the determination of changes in TC, LDL cholesterol, and HDL cholesterol (P-interaction = 0.007, 0.017, and 0.006, respectively). In the low-fat intake group (20% of energy derived from fat), carriers of the risk allele (G allele) exhibited greater reductions in TC and LDL cholesterol than did noncarriers (P = 0.036 and 0.039, respectively), whereas in the high-fat diet group (40% of energy derived from fat), participants with the G allele had a greater increase in HDL cholesterol than did participants without this allele (P = 0.038).

Conclusion: Our data showed better improvement in lipid profiles from long-term low-fat diet intake in the APOA5 rs964184 risk allele.

Trial registration: ClinicalTrials.gov NCT00072995.

Figures

FIGURE 1.

Effects of APOA5 rs964184 genotype and fat intervention on mean (±SE) changes in lipid profile at 2 y. Data included 219 and 176 (CC), 50 and 77 (CG), and 3 and 9 (GG) participants in low- and high-fat groups, respectively, at 2 y (total n = 534). P values were calculated by using general linear models with adjustment for age, sex, ethnicity, baseline BMI, baseline values for respective outcomes, and lipid-lowing medication use. HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; TC, total cholesterol; TG, triglyceride.

FIGURE 2.

Changes in TC and LDL-C in the low-fat diet intervention group according to APOA5 rs964184 genotype from baseline to 6 mo and 2 y under intervention. Data included 283, 250, and 219 (CC); 81, 65, and 50 (CG); and 4, 3, and 3 (GG) participants at baseline, 6 mo, and 2 y, respectively. P-interaction was tested by using linear mixed models between genotype and intervention time after adjustment for age, sex, ethnicity, baseline BMI, baseline values for respective outcomes, and lipid-lowing medication use. LDL-C, LDL cholesterol; TC, total cholesterol.