Journal of Molecular Medicine

, Volume 85, Issue 2, pp 119–128 | Cite as

APOA5 gene variation modulates the effects of dietary fat intake on body mass index and obesity risk in the Framingham Heart Study

  • Dolores Corella
  • Chao-Qiang Lai
  • Serkalem Demissie
  • L. Adrienne Cupples
  • Alisa K. Manning
  • Katherine L. Tucker
  • Jose M. OrdovasEmail author
Original Article


Diet is an important environmental factor interacting with our genes to modulate the likelihood of developing lipid disorders and, consequently, cardiovascular disease risk. Our objective was to study whether dietary intake modulates the association between APOA5 gene variation and body weight in a large population-based study. Specifically, we have examined the interaction between the APOA5–1131T>C and 56C>G (S19W) polymorphisms and the macronutrient intake (total fat, carbohydrate, and protein) in their relation to the body mass index (BMI) and obesity risk in 1,073 men and 1,207 women participating in the Framingham Offspring Study. We found a consistent and statistically significant interaction between the −1131T>C single-nucleotide polymorphism (SNP; but not the 56C>G) and total fat intake for BMI. This interaction was dose-dependent, and no statistically significant heterogeneity by gender was detected. In subjects homozygous for the −1131T major allele, BMI increased as total fat intake increased. Conversely, this increase was not present in carriers of the −1131C minor allele. Accordingly, we found significant interactions in determining obesity and overweight risks. APOA5–1131C minor allele carriers had a lower obesity risk (OR, 0.61, 95%; CI, 0.39–0.98; P = 0.032) and overweight risk (OR, 0.63, 95%; CI, 0.41–0.96; P = 0.031) compared with TT subjects in the high fat intake group (≥30% of energy ) but not when fat intake was low (OR, 1.16, 95%; CI, 0.77–1.74; P = 0.47 and OR = 1.15, 95%; CI, 0.77–1.71; P = 0.48) for obesity and overweight, respectively). When specific fatty acid groups were analyzed, monounsaturated fatty acids showed the highest statistical significance for these interactions. In conclusion, the APOA5–1131T>C SNP, which is present in approximately 13% of this population, modulates the effect of fat intake on BMI and obesity risk in both men and women.


APOA5 Obesity Body weight Fat intake Nutrigenetics 



This study was supported by the National Heart, Lung, and Blood Institute contract N01-HC-25195 and grant HL-54776, by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service, and by grants from the American Heart Association (0335432T) and the Spanish Ministerio de Educación y Ciencia (PR2006-0258) and the Spanish Ministeriode Sanidad (CB06/03/0035).


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Dolores Corella
    • 1
    • 2
  • Chao-Qiang Lai
    • 1
  • Serkalem Demissie
    • 3
  • L. Adrienne Cupples
    • 3
  • Alisa K. Manning
    • 3
  • Katherine L. Tucker
    • 1
  • Jose M. Ordovas
    • 1
    Email author
  1. 1.Nutrition and Genomics LaboratoryJM-USDA Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA
  2. 2.Department of Preventive MedicineUniversity of Valencia, Genetic and Molecular Epidemiology UnitValenciaSpain
  3. 3.Department of BiostatisticsBoston University School of Public HealthBostonUSA

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