Effect of Apolipoprotein E Polymorphism on Serum Lipid, Lipoproteins, and Atherosclerosis in Hemodialysis Patients Galip Gu ¨ z, MD, F. Nurhan O ¨ zdemir, MD, Siren Sezer, MD, I ˙ clal Is ¸ iklar, MD, Zu ¨ beyde Arat, MD, Mu ¨ nire Turan, PhD, and Mehmet Haberal, MD ● Atherosclerosis and cardiovascular disease are the main causes of death in hemodialysis patients. Possession of the apolipoprotein E4 (ApoE4) allele has been associated with increased levels of serum lipids and with coronary and carotid artery atherosclerosis. We investigated the possible relationship between ApoE polymorphism and atherosclerosis risk factors in hemodialysis patients. Two hundred sixty-nine hemodialysis patients (115 women, 154 men) were included in our study. The mean patient age and mean hemodialysis duration were 45.8  15.3 years and 52.6  40.6 months, respectively. Testing was done on all patients to determine ApoE genotype and serum levels of total cholesterol (T-Cho), low-density lipoprotein (LDL-C), high-density cholesterol (HDL-C), triglyceride (TG), lipoprotein (a) (Lp[a]), intact parathormone (iPTH), and fibrinogen. ApoE genotype was identified with the polymerase chain reaction. Ultrasonographic measurement of carotid artery intima media thickness (IMT) was used to diagnose atherosclerosis. We also analyzed ApoE polymorphism and risk factors such as age, gender, duration of hemodialysis, smoking, and hypertension in relation to the presence of atherosclerosis. Serum T-Cho and LDL-C levels were higher in patients with the ApoE4/3 phenotype than in those with ApoE3/3 and ApoE3/2 phenotypes (P < 0.05). However, there was no statistically significant link between ApoE polymorphism and serum levels of TG, HDL-C, or Lp(a) (P > 0.05). Apart from a relationship with age and duration of hemodialysis (P < 0.05), we found no significant association between atherosclerosis and ApoE polymorphism or the other risk factors analyzed (P > 0.05). In conclusion, although ApoE polymorphism significantly affects serum levels of T-Cho and LDL-C in hemodialysis patients, this study indicates that ApoE polymorphism is not associated with the presence of atherosclerosis in these individuals. The high incidence of atherosclerosis in these patients underlines the need for further research on other possible causative factors. © 2000 by the National Kidney Foundation, Inc. INDEX WORDS: Apolipoprotein E (ApoE); atherosclerosis; hemodialysis; lipids; lipoprotein (a). A THEROSCLEROTIC vascular disease is the main cause of death among patients on maintenance hemodialysis. 1-8 Although it is ac- cepted that uremia accelerates atherosclerosis, the pathophysiologic mechanisms responsible for this complication are unknown. Many factors have the potential to promote atherosclerosis, including hypercholesterolemia, hypertriglyceri- demia, hyperlipoproteinemia, decreased serum high-density cholesterol (HDL-C), hyperten- sion, hyperparathyroidism, and smoking. 9 How- ever, what we know about the classic risk factors does not explain all atherosclerotic vascular com- plications. Thus, other possible factors need to be investigated. Apolipoprotein E (ApoE) is a ligand for the low-density lipoprotein (LDL) family of recep- tors and plays a pivotal role in cholesterol metab- olism. In the normal population, three ApoE alleles (2, 3, and 4) produce the ApoE iso- forms ApoE2, ApoE3, and ApoE4. Interchanges of cysteine and arginine at positions 112 and 158 of the ApoE molecule, which contains 299 amino acids, account for the differences in the ApoE isoforms. Six possible ApoE phenotypes are gen- erated from these isoforms: ApoE2/2, ApoE2/3, ApoE2/4, ApoE3/3, ApoE3/4, and ApoE4/4. Many studies in the nonuremic population have shown that ApoE modulates lipid metabolism and that possession of the 4 allele is related to hyperlipidemia and to coronary and carotid ar- tery atherosclerosis. 10-14 However, the relation- ship between ApoE polymorphism and lipid lev- els, lipoprotein metabolism, and atherosclerosis has been investigated in only a small number of hemodialysis patients. 15 The aim of our study was to assess the impact of ApoE polymorphism and other factors on atherosclerotic vascular disease in hemodialysis patients. We also examined the association be- tween ApoE polymorphism and lipid profile and From the Departments of Nephrology and Immunology, and the Hemodialysis Unit, Baskent University Faculty of Medicine, Ankara, Turkey. Received October 20, 1999; accepted in revised form May 5, 2000. Address reprint requests to Galip Gu ¨z, MD, Department of Nephrology, Baskent University Faculty of Medicine, Fevzi C ¸ akmak Bulvari 10. Sokak No: 45, Bahc ¸elievler, Ankara, 06490, Turkey. E-mail: galip_guz@hotmail.com © 2000 by the National Kidney Foundation, Inc. 0272-6386/00/3604-0021$3.00/0 doi:10.1053/ajkd.2000.17682 American Journal of Kidney Diseases, Vol 36, No 4 (October), 2000: pp 826-836 826