APOA5 gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerides in a Mediterranean population

J Nutr. 2011 Mar;141(3):380-5. doi: 10.3945/jn.110.130344. Epub 2011 Jan 5.


APOA5 is one of the strongest regulators of plasma TG concentrations; nevertheless, its mechanisms of action are poorly characterized. Genetic variability at the APOA5 locus has also been associated with increased cardiovascular disease risk; however, this predisposition could be attenuated in the context of a prudent diet as traditionally consumed in the Mediterranean countries. We have investigated the interaction between a single nucleotide polymorphism (SNP) at the APOA5 gene (-1131T > C) and dietary fat that may modulate TG-rich lipoprotein concentrations and anthropometric measures in overweight and obese participants. We recruited 1465 participants from a Spanish population (20-65 y old; BMI 25-40 kg/m(2)) attending outpatient obesity clinics. Consistent with previous reports, we found an association between the APOA5-1131T > C SNP and TG-rich lipoprotein concentrations that were higher in carriers of the minor allele than in noncarriers (P < 0.001). Moreover, we found a significant genotype-dietary fat interaction for obesity traits. Participants homozygous for the -1131T major allele had a positive association between fat intake and obesity, whereas in those carrying the APOA5-1131C minor allele, higher fat intakes were not associated with higher BMI. Likewise, we found genotype-dietary fat interactions for TG-rich lipoproteins (P < 0.001). In conclusion, we have replicated previous gene-diet interactions between APOA5 -1131T > C SNP and fat intake for obesity traits and detected a novel interaction for TG-rich lipoprotein concentrations. Our data support the hypothesis that the minor C-allele may protect those consuming a high-fat diet from obesity and elevated concentrations of TG-rich lipoproteins.

Publication types

  • 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
  • Aged
  • Apolipoprotein A-V
  • Apolipoproteins A / genetics*
  • Body Mass Index
  • Cardiovascular Diseases / epidemiology
  • Dietary Fats / adverse effects*
  • Female
  • Genetic Association Studies
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / epidemiology*
  • Hypertriglyceridemia / genetics*
  • Lipoproteins / blood
  • Lipoproteins, VLDL / blood
  • Male
  • Mediterranean Region
  • Middle Aged
  • Obesity / blood
  • Obesity / epidemiology*
  • Obesity / genetics*
  • Overweight / epidemiology
  • Overweight / genetics
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Risk Factors
  • Spain / epidemiology
  • Triglycerides / blood
  • Young Adult


  • APOA5 protein, human
  • Apolipoprotein A-V
  • Apolipoproteins A
  • Dietary Fats
  • Lipoproteins
  • Lipoproteins, VLDL
  • Triglycerides
  • lipoprotein triglyceride