ISSN 0026-8933, Molecular Biology, 2008, Vol. 42, No. 6, pp. 829–833. © Pleiades Publishing, Inc., 2008. Original Russian Text © R. Chaaba, N. Attia, S. Hammami, M. Smaoui, K. Ben Hamda, S. Mahjoub, M. Hammami, 2008, published in Molekulyarnaya Biologiya, 2008, Vol. 42, No. 6, pp. 931–937. 829 1 INTRODUCTION Human apolipoprotein E (Apo E) is a normal con- stituent of very low-density lipoproteins (VLDL), high-density lipoproteins (HDL), intermediate-den- sity lipoproteins (IDL), chylomicrons, and chylomi- cron remnants. The apo E lets the hepatic receptors for Apo E bind and remove chylomicrons. Also, it medi- ates the LDL transport cholesterol to the liver [1]. Its gene is polymorphic with three alleles, apo E2, apo E3, and apo E4. E3 is the most common allele. The alleles translate into three isoforms of the protein [2]. These isoforms differ from each other only by single amino acid substitutions at positions 112 and 158, but have profound physiological consequences. The iso- forms vary in their receptor-binding activity. The E4 isoform has high affinity for the apo E receptor, whereas E2 isoform has a decreased affinity [3]. The Apo E polymorphism was shown to be associated with lipid and lipoprotein content variations [4, 5]. The E4 allele is associated with elevated LDLcholesterol con- centration [6, 7]. The associations between Apo E 1 The text was submitted by the authors in English. genotypes and plasma triglyceride level and HDLcho- lesterol concentration are controversial [6, 8, 9]. A recent study showed gene–gene (Apo E-CETP) inter- actions in determining plasma HDLcholesterol con- centrations in men and women from the Southern European population [10]. Also, Djousse et al. have reported a gene–environment interaction between the Apo E polymorphism and alcohol intake on plasma HDLcholesterol concentrations [11]. However, the metabolic pathway was not examined. In fact, Apo E is one factor, among many others, that participates in the lipoprotein metabolism. The CETP is a key protein in the reverse cholesterol transport. It facilates the transport of cholesteryl ester and triglycerides between lipoproteins [12]. It picks up cholesteryl ester from HDL to Apo B-containing lipoprotein and can exchange them for triglycerides (and vice versa). The transfer of cholesterol transfer required the presence of Apo E [13]. Many studies showed that the CETP influences the plasma C-HDL concentrations [14, 15] and that the CETP activity or expression is modulated by lipid or lipoprotein content variation. GENOMICS-TRANSCRIPTOMICS-PROTEOMICS The Effect of Apolipoprotein E Polymorphism on Plasma Cholesteryl Ester Transfer Protein Activity in Type 2 Diabetic Patients 1 R. Chaaba a , N. Attia a , S. Hammami b , M. Smaoui a , K. Ben Hamda c , S. Mahjoub b , and M. Hammami a a Biochemistry Laboratory, UR 08–39, Faculty of Medicine 5019 Monastir, Tunisia b Department of Internal Medicine, 5019 Monastir, Tunisia c Department of Cardiology, CHU Monastir, Tunisia e-mail: rchaaba@yahoo.fr Received September 05, 2007; in final form, November 26, 2007 Abstract—We studied the relationship between apo E polymorphism and cholesteryl ester transfer protein (CETP) activity in 127 type 2 diabetic patients who did not take lipid lowering drugs. Furthermore, we studied the relationship between apo E and cholesteryl ester transfer protein (CETP) in modulating plasma triglyceride and HDLcholesterol. Apo E genotypes were determined by PCR-RFLP, and CETP activity was measured using an exogenous way. Our results showed that the CETP activity increased significantly in the E2 carrier group compared to E4 carriers and E3E3 homozygous (84.7 ± 43.9 vs. 62.5 ± 35.9 vs. 52.6 ± 23.6 nmol CE/ml/2h, respectively; p = 0.015). However, there was no association between apo E polymorphism and lipid parameter variations. Even after adjustment for CETP activity, the results remained unchanged, showing that CETP did not step in the relationship between apo E and lipid parameter variations. In conclusion there is an association between apo E polymorphism and CETP activity, and this association did not affect the relationship between apo E polymorphism and triglyceride and HDLcholesterol concentrations. DOI: 10.1134/S0026893308060010 Key words: apolipoprotein E (Apo E), cholesteryl ester transfer protein (CETP), HDLcholesterol, polymor- phism, triglycerides, Tunisian, Type 2 diabetes. UDC 618.19