Cholesteryl ester transfer protein gene variations and macronutrient intakes interaction in relation to metabolic syndrome: Tehran lipid and glucose study

Document Type: Original Article


1 Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Objective(s): There are controversial results regarding the effect of the interaction of CETP polymorphisms with dietary fats on the lipid profiles. The aim of this study was to examine the effect of CETP polymorphisms (rs5882 and rs3764261) and macronutrient intakes interaction in relation to metabolic syndrome (MetS) or its components.
Materials and Methods: In this nested case-control study, subjects were selected from among participants of the Tehran Lipid and Glucose Study. Cases (n=441) were individually matched with two controls (844 non-MetS subjects). DNA samples were genotyped with HumanOmniExpress-24-v1-0 bead chips, including 649,932 SNP loci.
Results: The mean ages at baseline were 38.1±10 and 37.0±10 years in women and 36.2±11 and 36.3±11 years in men, respectively in cases and controls. We did not find significant gene-diet interactions between rs5882 and dietary macronutrient intakes in relation to MetS risk. The risk of low HDL-C was lower in the first quartile of MUFA and total fat intake in G allele carriers, compared to AA genotype group. The risk of high BP appeared to increase significantly in higher quartiles of trans-fatty acid intakes (>1.81% of total energy intake) in G allele carriers compared with the AA genotype group. No significant interactions were found between rs3764261 and macronutrient intakes in association with MetS or its components.
Conclusion: Our findings demonstrate that dietary fats modify the association of rs5882 and risk of low HDL-C and high blood pressure.


Main Subjects

1. Delavari A, Forouzanfar MH, Alikhani S, Sharifian A, Kelishadi R. First nationwide study of the prevalence of the metabolic syndrom and optimal cutoff points of waist circumference in the Middle East: the national survey of risk factors for noncommunicable diseases of Iran. Diabetes care 2009;32:1092-1097.
2. Azizi F, Ghanbarian A, Momenan AA, Hadaegh F, Mirmiran P, Hedayati M, et al. Prevention of non-communicable disease in a population in nutrition transistion: Tehran Lipid and Glucose Study phase II. Trials 2009;10:5.
3. Hosseini-Esfahani F, Jessri M, Mirmiran P, Bastan S, Azizi F. Adherence to dietary recommendations and risk of metabolic syndrome: Tehran Lipid and Glucose Study. Metab Clin Exp 2010;59:1833-1842.
4. Qi Q, Durst R, Schwarzfuchs D, Leitersdorf E, Shpitzen S, Li Y, et al. CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials. J Lipid Res 2015;56:713-721.
5. Phillips CM. Nutrigenetics and metabolic disease: current status and implications for personalised nutrition. Nutrients 2013;5:32-57.
6. Thompson A, Di Angelantonio E, Sarwar N, Erqou S, Saleheen D, Dullaart RP, et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 2008;299:2777-2788.
7. Boekholdt SM, Sacks FM, Jukema JW, Shepherd J, Freeman DJ, McMahon AD, et al. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation 2005;111:278-287.
8. Garcia-Rios A, Alcala-Diaz JF, Gomez-Delgado F, Delgado-Lista J, Marin C, Leon-Acuna A, et al. Beneficial effect of CETP gene polymorphism in combination with a Mediterranean diet influencing lipid metabolism in metabolic syndrome patients: CORDIOPREV study. Clin Nutr 2018; 37:229-234.
9. Mackay DS, Eck PK, Rideout TC, Baer DJ, Jones PJ. Cholesterol ester transfer protein polymorphism rs5882 is associated with triglyceride-lowering in response to plant sterol consumption. Appl Physiol Nutr Metab 2015;40:846-849.
10. Darabi M, Abolfathi A, Noori M, Kazemi A, Ostadrahimi A, Rahimipour A, et al. Cholesteryl ester transfer protein I405V polymorphism influences apolipoprotein AI response to a change in dietary fatty acid composition. Appl Physiol Nutr Metab 2009;41:554-558.
11. Terán-García M, Després J-P, Tremblay A, Bouchard C. Effects of cholesterol ester transfer protein (CETP) gene on adiposity in response to long-term overfeeding. Atherosclerosis 2008;196:455-460.
12. Frances E, Carrasco P, Sorli JV, Ortega C, Portoles O, Rubio MM, et al. Impact of APOE, APOA5 and CETP polymorphism on plasma lipid concentrations and response to a mediterranean diet in the predimed study. Atherosclerosis Suppl 2006;7:47.
13. Aitken WAE, Chisholm AWAH, Duncan AW, Harper MJ, Humphries SE, Mann JI, et al. Variation in the cholesteryl ester transfer protein (CETP) gene does not influence individual plasma cholesterol response to changes in the nature of dietary fat. Nutr Metab Cardiovasc Dis 2006;16:353-363.
14. Friedlander Y, Leitersdorf E, Vecsler R, Funke H, Kark J. The contribution of candidate genes to the response of plasma lipids and lipoproteins to dietary challenge. Atherosclerosis 2000;152:239-248.
15. Wallace AJ, Humphries SE, Fisher RM, Mann JI, Chisholm A, Sutherland WH. Genetic factors associated with response of LDL subfractions to change in the nature of dietary fat. Atherosclerosis 2000;149:387-394.
16. Li TY, Zhang C, Asselbergs FW, Qi L, Rimm E, Hunter DJ, et al. Interaction between dietary fat intake and the cholesterol ester transfer protein TaqIB polymorphism in relation to HDL-cholesterol concentrations among US diabetic men. Am J Clin Nutr 2007;86:1524-1529.
17. Mirmiran P, Hosseini Esfahani F, Mehrabi Y, Hedayati M, Azizi F. Reliability and relative validity of an FFQ for nutrients in the Tehran Lipid and Glucose Study. Public Health Nutr 2010;13:654-662.
18. Delshad M, Ghanbarian A, Ghaleh NR, Amirshekari G, Askari S, Azizi F. Reliability and validity of the modifiable activity questionnaire for an Iranian urban adolescent population. Int J Prev Med 2015;6:3.
19. Kriska AM, Knowler WC, LaPorte RE, Drash AL, Wing RR, Blair SN, et al. Development of questionnaire to examine relationship of physical activity and diabetes in Pima Indians. Diabetes care 1990;13:401-411.
20. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000;32:S498-504.
21. Daneshpour MS, Fallah MS, Sedaghati-Khayat B, Guity K, Khalili D, Hedayati M, et al. Rationale and Design of a Genetic Study on Cardiometabolic Risk Factors: Protocol for the Tehran Cardiometabolic Genetic Study (TCGS). 2017;6:e28.
22. Grundy SM, Hansen B, Smith SC, Cleeman JI, Kahn RA. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Arterioscler Thromb Vasc Biol 2004;24:e19-24.
23. Azizi F, Hadaegh F, Khalili D, Esteghamati A, Hosseinpanah F, Delavari A, et al. Appropriate definition of metabolic syndrome among Iranian adults: report of the Iranian National Committee of Obesity. Arch Iran Med 2010;13:426-428.
24. Rudkowska I, Dewailly E, Hegele RA, Boiteau V, Dube-Linteau A, Abdous B, et al. Gene-diet interactions on plasma lipid levels in the Inuit population. Br J Nutr 2013;109:953-961.
25. Cheema SK, Agarwal-Mawal A, Murray CM, Tucker S. Lack of stimulation of cholesteryl ester transfer protein by cholesterol in the presence of a high-fat diet. J Lipid Res 2005;46:2356-2366.