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

Am J Clin Nutr. 2012 Oct;96(4):917-22. doi: 10.3945/ajcn.112.040907. Epub 2012 Aug 22.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Apolipoprotein A-V
  • Apolipoproteins A / genetics*
  • Apolipoproteins A / metabolism
  • Body Mass Index
  • Diet, Fat-Restricted / adverse effects
  • Diet, High-Fat / adverse effects
  • Diet, Reducing* / adverse effects
  • Follow-Up Studies
  • Genome-Wide Association Study
  • Heterozygote
  • Humans
  • Hyperlipidemias / etiology
  • Hyperlipidemias / prevention & control*
  • Lipids / blood*
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / diet therapy
  • Obesity / genetics
  • Overweight / blood
  • Overweight / diet therapy*
  • Overweight / genetics*
  • Overweight / physiopathology
  • Polymorphism, Single Nucleotide*
  • Risk
  • United States
  • Weight Loss


  • APOA5 protein, human
  • Apolipoprotein A-V
  • Apolipoproteins A
  • Lipids

Associated data

  • ClinicalTrials.gov/NCT00072995