Humans, Clinical 554 Darabi M et al. Diet Effect on CETP I405V Genotypes … Horm Metab Res 2009; 41: 554–558 received 25.10.2008 accepted 07.01.2009 Bibliography DOI 10.1055/s-0029-1192034 Published online: February 25, 2009 Horm Metab Res 2009; 41: 554–558 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence M. Darabi Department of Biochemistry School of Medicine Tabriz University (Medical Sciences) Golgasht Avenue Tabriz Iran Tel: + 98/411/336 46 66 Fax: + 98/411/336 46 66 mdarabi@hotmail.com Key words ● ▶ gene-nutrient interaction ● ▶ high density lipoprotein ● ▶ CETP ● ▶ apoA-I Cholesteryl Ester Transfer Protein I405V Polymorphism Influences Apolipoprotein A-I Response to a Change in Dietary Fatty Acid Composition ment [6]. The activity of CETP was shown to be affected by the phospholipid content of HDL par- ticles [7] and dietary fatty acid composition [8]. CETP I405V is a very common SNP (rs5882) aris- ing from A →G transition in exon 14, which lead a missense mutation with the substitution of valine for isoleusine at codon 405 [9]. Observa- tional studies of the CETP I405V polymorphism have shown either no association with the risk of coronary heart disease (CHD) or lipid parameters [10, 11] or higher HDL-C levels and elevated risk of CHD for the V allele homozygotes [3]. The I405V variant is also a determinant of circulating CETP [9]. Despite intense study, it is still unclear whether, how, and under which circumstances this CETP gene variation affects CHD risk status [12]. According to recent findings I405V CETP varia- tion increases the adverse effect of excessive cal- orie consumption on adiposity and HDL-C levels [13]. This suggested that subjects with different genotypes of I405V polymorphism may respond differently to dietary fatty acid composition. To test this hypothesis, the effect of a modification in the ratio of polyunsaturated to saturated fatty Introduction & Genetic factors play a major role in susceptibility to common diseases such as cardiovascular dis- eases, type 2 diabetes, and obesity. Genetic varia- tions can influence the levels of the gene product or affect the response of phenotypes to environ- mental factors, including diet [1]. Dyslipidemia is an established risk factor for cardiovascular dis- eases, one of the leading causes of death in many parts of the world [2]. Apart from being a source of energy, dietary fatty acids are known to affect various aspects of lipoprotein metabolism, which makes the evaluation of their metabolic effects even more important. The cholesteryl ester transfer protein (CETP), a hydrophobic glycoprotein mediates the transfer of cholesteryl esters from HDL to apolipoprotein B-containing particles [3]. The critical role of CETP in lipoprotein metabolism has been con- firmed by high concentrations of HDL cholesterol (HDL-C) observed in patients with genetic CETP deficiency [4]. However, recent results of clinical trials showed that drug-induced CETP inhibition produced negative outcome in humans [5]. It has been suggested that the effects of CETP inhibitors may critically depend on the metabolic environ- Authors M. Darabi 1 , A. A. Abolfathi 1 , M. Noori 1 , A. Kazemi 2 , A. Ostadrahimi 2 , A. Rahimipour 1 , M. Darabi 3 , K. Ghatrehsamani 1 Affiliations 1 Department of Biochemistry, School of Medicine, Tabriz University (Medical Sciences), Tabriz, Iran 2 Nutritional Research Center, Tabriz University (Medical Sciences), Tabriz, Iran 3 Department of Biochemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran Abstract & The aim of the present study was to investi- gate whether the cholesteryl ester transfer pro- tein (CETP) I405V polymorphism modifies the response to changes in the dietary ratio of poly- unsaturated to saturated fat (P:S). The population included 85 healthy subjects with the different I405V genotypes (35 II, 36 IV, and 14 VV) assigned to two consecutive 28-day experimental period. All subjects consumed a high-P:S with P:S of 1.2 for the first period and a low-P:S with a P:S of 0.3 for the next 28-day period. At the first and end of each dietary period, serum lipid, lipoprotein, and CETP concentrations were measured. At screen- ing, lipid or lipoprotein concentrations were not significantly different among CETP I405V geno- type groups. After the low-P:S diet, subjects car- rying V allele had greater reduction in apoA-I and HDL cholesterol (HDL-C) than subjects with II genotype. A genotype-by-diet interaction effect was observed on apoA-I (p = 0.016) concentra- tions. In conclusion, the CETP I405V polymor- phism contributes to the unfavorable changes of apoA-I and HDL-C when a high-P:S diet was replaced with a low-P:S diet.