Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population |
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Authors: | Dolores Corella Paula Carrasco Montserrat Fitó Miguel Angel Martínez-González Jordi Salas-Salvadó Fernando Arós José Lapetra Marisa Guillén Carolina Ortega-Azorín Julia Warnberg Miquel Fiol Valentina Ruiz-Gutierrez Lluís Serra-Majem J Alfredo Martínez Emilio Ros Ramón Estruch |
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Institution: | 1. Department of Preventive Medicine and Public Health,School of Medicine, University of Valencia, Valencia, Spain;2. CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain;4. Cardiovascular Epidemiology Unit, Municipal Institut for Medical Research, Barcelona, Spain;7. Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra, Navarra, Spain;11. Human Nutrition Unit, Faculty of Medicine, IISPV, University Rovira i Virgili, Reus, Spain;8. Department of Cardiology, Hospital Txagorritxu, Vitoria, Spain;71. Department of Family Medicine, San Pablo Health Center, Primary Care Division of Sevilla, Sevilla, Spain;112. Department of Epidemiology, School of Medicine, University of Malaga, Malaga, Spain;77. University Institute for Health Sciences Investigation, Hospital Son Dureta, Palma de Mallorca, Spain;1111. Instituto de la Grasa, Consejo Superior de Investigaciones Científicas, Sevilla, Spain;88. Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain;771. Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona, Spain;11112. Department of Nutrition, Lipid Clinic, Endocrinology and Nutrition Service;884. Department of Internal Medicine, Hospital Clinic, Institut d''Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain |
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Abstract: | Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the −4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D''= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors. |
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Keywords: | lipids nutrigenetics Mediterranean diet fat alcohol obesity |
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