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

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Abstract

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.

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Acknowledgment

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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Authors and Affiliations

  1. Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA, 02111-1524, USA

    Dolores Corella, Chao-Qiang Lai, Katherine L. Tucker & Jose M. Ordovas

  2. Department of Preventive Medicine, University of Valencia, Genetic and Molecular Epidemiology Unit, Valencia, Spain

    Dolores Corella

  3. Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, MA, 02118, USA

    Serkalem Demissie, L. Adrienne Cupples & Alisa K. Manning

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  1. Dolores Corella
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  2. Chao-Qiang Lai
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  7. Jose M. Ordovas
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Correspondence to Jose M. Ordovas.

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Corella, D., Lai, CQ., Demissie, S. et al. APOA5 gene variation modulates the effects of dietary fat intake on body mass index and obesity risk in the Framingham Heart Study. J Mol Med 85, 119–128 (2007). https://doi.org/10.1007/s00109-006-0147-0

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  • DOI: https://doi.org/10.1007/s00109-006-0147-0

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