Beneficial effect of CETP gene polymorphism in combination with a Mediterranean diet influencing lipid metabolism in metabolic syndrome patients: CORDIOPREV study

Authors: GARCIA-RIOS, ANTONIO - Universidad De Cordoba; ALCALA-DIAZ, JUAN - Universidad De Cordoba; GOMEZ-DELGADO, FRANCISCO - Universidad De Cordoba; DELGADO-LISTA, JAVIER - Universidad De Cordoba; MARIN, CARMEN - Universidad De Cordoba; LEON-ACUNA, ANA - Universidad De Cordoba; CAMARGO, ANTONIO - Universidad De Cordoba; RODRIGUEZ-CANTALEGO, FERNANDO - Universidad De Cordoba; BLANCO-ROJO, RUTH - Universidad De Cordoba; QUINTANA-NAVARRO, GRACIA - Universidad De Cordoba; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PEREZ-JIMENEZ, FRANCISCO - Universidad De Cordoba; LOPEZ-MIRANDO, JOSE - Universidad De Cordoba; PEREZ-MARTINEZ, PABLO - Universidad De Cordoba

Submitted to: Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/11/2016
Publication Date: 12/24/2016
Citation: Garcia-Rios, A., Alcala-Diaz, J.F., Gomez-Delgado, F., Delgado-Lista, J., Marin, C., Leon-Acuna, A., Camargo, A., Rodriguez-Cantalego, F., Blanco-Rojo, R., Quintana-Navarro, G., Ordovas, J.M., Perez-Jimenez, F., Lopez-Mirando, J., Perez-Martinez, P. 2016. Beneficial effect of CETP gene polymorphism in combination with a Mediterranean diet influencing lipid metabolism in metabolic syndrome patients: CORDIOPREV study. Clinical Nutrition. doi: 10.1016/j.clnu.2016.12.011.

Interpretive Summary: Circulating blood lipids are commonly used as markers of cardiovascular risk. Therefore, better knowledge about how they are regulated by endogenous (i.e. genetic) and exogenous (i.e. diet) factors will be paramount to achieving healthy levels of blood lipids and preventing cardiovascular diseases. One of the genetic factors associated with circulating lipids, and more specifically the HDL-C and triglycerides, is the cholesteryl ester transfer protein (CETP) gene. This gene has a common variant known as rs3764261, and it is present in two different forms: a more common form (G) or a less common form (T). We investigated whether two different dietary patterns (Mediterranean diet or low-fat diet) interacted with the CETP rs3764261 variant to modulate blood levels of HDL-C and triglycerides. We did this for 424 subjects with metabolic syndrome participating in the CORDIOPREV Study. We found significant gene-diet interactions between the rs3764261 variant and the dietary pattern for HDL-C and triglyceride concentrations. Specifically, after being on a Mediterranean diet for 12 months, subjects who carried the minor T form had higher blood HDL-C concentrations and lower triglycerides compared to those who were homozygous for the major allele. In contrast, in the low-fat intervention group, no significant differences were found between subjects carrying the different CETP genotypes after 12 months of dietary treatment. Our data support the notion that the consumption of a Mediterranean diet provides greater health benefits to subjects who both carry the minor form at the CETP rs3764261 variant and who are at risk for cardiovascular disease. These results contribute to the body of evidence supporting the benefits of personalized nutrition.

Technical Abstract: The cholesteryl ester transfer protein (CETP) gene has been implicated in high-density lipoprotein (HDL-C) metabolism. However, little is known about the impact of this gene on metabolic syndrome (MetS) patients and its interaction with diet. Here, we evaluate whether the consumption of a Mediterranean diet, compared with a Low-fat diet, interacts with the rs3764261 SNP at the CETP locus to modify lipid metabolism in MetS patients. Plasma lipid concentrations and rs3764261 genotypes were determined in 424 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% MUFA) vs Low-fat diet (28% fat, 12% MUFA)). We found significant gene-diet interactions between rs3764261 SNP and the dietary pattern for HDL-C (P = 0.006) and triglyceride concentrations (P = 0.040). Specifically, after 12 months of Mediterranean diet intervention, subjects who were carriers of the minor T allele (TT + TG) displayed higher plasma HDL-C concentrations (P = 0.021) and lower triglycerides (P = 0.020) compared with those who were homozygous for the major allele (GG). In contrast, in the Low-fat intervention group, no significant differences were found between CETP genotypes after 12 months of dietary treatment. Our data support the notion that the consumption of a Mediterranean diet may play a contributing role in triggering lipid metabolism by interacting with the rs3764261 SNP at CETP gene locus in MetS patients. Due to the complex nature of gene-environment interactions, dietary adjustment in MetS patients may require a personalized approach.