|Corella, Dolores -|
|Arnett, Donna -|
|Tucker, Katherine -|
|Kabagambe, Edmond -|
|Tsai, Michael -|
|Lai, Chao Qiang|
|Lee, Yu-Chi -|
|Warodomwichit, Daruneewan -|
|Hopkins, Paul -|
|Ordovas, Jose -|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 26, 2011
Publication Date: December 1, 2011
Citation: Corella, D., Arnett, D.K., Tucker, K.L., Kabagambe, E.K., Tsai, M.Y., Parnell, L.D., Lai, C., Lee, Y., Warodomwichit, D., Hopkins, P.N., Ordovas, J.M. 2011. A high intake of saturated fatty acids strengthens the association between the fat mass and obesity-associated gene and BMI. Journal of Nutrition. 141(12):2219-2225. Interpretive Summary: Much evidence has been collected indicating the importance of the FTO gene in obesity, particularly in the clinical measure of body mass index, or BMI. However, it is not known if dietary and lifestyle factors can modulate the genetic link between variants of the FTO gene and BMI. The objective of this study was to investigate whether such modulations exist by looking at commonly occurring variants of the FTO gene in two populations – one of predominately White Americans living in Utah or Minnesota, the other of Puerto Ricans from the Boston area. We assessed energy and nutrient intake, and physical activity using validated questionnaires. In the population of White Americans we observed that exercise modulates the FTO-BMI link, but this was not seen in the Puerto Ricans. We also found in both populations a significant relationship between intake of saturated fat acting on the FTO-BMI link such that persons with two copies of the FTO variant conferring risk of obesity had a higher BMI only when the intake of saturated fats was above the population mean. In other words, the risk for a higher BMI does not show itself in those persons carrying the at-risk version of the FTO gene until their intake of saturated fat rises above the average intake. Such relationships were not observed for carbohydrate intake.
Technical Abstract: Evidence that physical activity (PA) modulates the association between the fat mass and obesity-associated gene (FTO) and BMI is emerging; however, information about dietary factors modulating this association is scarce. We investigated whether fat and carbohydrate intake modified the association of FTO gene variation with BMI in two populations, including participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 1069) and in the Boston Puerto Rican Health (BPRHS) study (n = 1094).We assessed energy, nutrient intake, and PA using validated questionnaires. Genetic variability at the FTO locus was characterized by polymorphisms rs9939609 (in the GOLDN) and rs1121980 (in the GOLDN and BPRHS). We found significant interactions between PA and FTO on BMI in the GOLDN but not in the BPRHS. We found a significant interaction between SFA intake and FTO on BMI, which was stronger than that of total fat and was present in both populations (P-interaction = 0.007 in the GOLDN and P-interaction = 0.014 in BPRHS for categorical; and P-interaction = 0.028 in the GOLDN and P-interaction = 0.041 in BPRHS for continuous SFA). Thus, homozygous participants for the FTO-risk allele had a higher mean BMI than the other genotypes only when they had a high-SFA intake (above the population mean: 29.7 +/- 0.7 vs. 28.1+/- 0.5 kg/m2; P = 0.037 in the GOLDN and 33.6+/-0.8 vs. 31.2 +/-0.4 kg/m2; P = 0.006 in BPRHS). No associations with BMI were found at lower SFA intakes. We found no significant interactions with carbohydrate intake. In conclusion, SFA intake modulates the association between FTO and BMI in American populations.