ISSN: 0886-022X (print), 1525-6049 (electronic)
Ren Fail, 2014; 36(10): 1504–1509
!2014 Informa Healthcare USA, Inc. DOI: 10.3109/0886022X.2014.949760
CLINICAL STUDY
Association of apolipoprotein E gene polymorphism with end-stage renal disease and hyperlipidemia in patients on long-term hemodialysis
Hanaaˆ Lahrach
1,2, Fadwa Essiarab
1, Mohammed Timinouni
3, Bachir Hatim
2, Salma El Khayat
4, Loubna Er-Rachdi
4, Jamal Jarir
5, Anas Kettani
1, Noreddine Ghalim
5, Hassan Taki
1, Halima Lebrazi
1, Benyounes Ramdani
4, and
Rachid Saı¨le
1
1
Faculty of Sciences Ben M’sik, Laboratory of Biology and Health, Hassan II University, Casablanca, Morocco,
2Pasteur Laboratory of Biomedical Analysis, Settat, Morocco,
3Research Department, Laboratory of Molecular Biology, Pasteur Institute of Morocco, Casablanca, Morocco,
4Nephrology and Hemodialysis Center, UHC Ibn Rochd, Casablanca, Morocco, and
5Research Department, Laboratory of Biochemistry, Pasteur Institute of Morocco, Casablanca, Morocco
Abstract
Background: Cardiovascular diseases (CVDs) are the leading cause of death of patients with chronic renal failure. Apolipoprotein E (apoE) plays an important role in the homeostasis of cholesterol and triglycerides. Objective: We aimed to investigate the possible link(s) between apoE gene polymorphism, inflammation and lipoproteins in hemodialysis patients. Methods: We studied 109 end-stage renal disease (ESRD) patients and 97 controls. The serum lipids, apolipoproteins, lipoprotein particles, high-sensitivity C-reactive protein (hs-CRP) and total homocysteine (t-Hcy) levels and paraoxonase (PON) activity were determined in our patients.
We also analyzed apoE gene polymorphism in the patients and controls. Results: The analysis of the apoE gene demonstrated a predominance of the e3 allele in both the patients and controls, followed by the e4 and then the e2 alleles. The analysis of the apoE genotype and allele frequencies showed significantly higher e4 allele and E3E4 genotype frequencies and decreased e3 allele and E3E3 genotype frequencies in the patients compared with the controls. The e2, e4 and E3E4 carriers within the ESRD patient population presented an atherogenic lipid profile. However, there were no significant variations in the serum PON activity and the hs-CRP and t-Hcy levels between individuals with different apoE polymorph- isms. Conclusions: Our findings suggest an association between the e4 allele, E3E4 genotype and ESRD. The apoE polymorphism affects the serum lipoprotein levels, and the ESRD patients who are e4 and e2 allele carriers are more likely to present an atherogenic lipoprotein profile that may be a major factor associated with increased risk of CVD.
Keywords
ApoE polymorphism, apolipoproteins, cardiovascular risk, end-stage renal disease, inflammation, lipids
History
Received 18 April 2014 Revised 12 July 2014 Accepted 15 July 2014
Published online 21 August 2014
Introduction
Atherosclerotic vascular diseases are the leading cause of death among dialysis patients. Chronic renal insufficiency (CRI) is classified as a risk factor of vascular events.
Dyslipidemia, malnutrition, oxidant stress and inflammation have been reported as specific vascular risk factors that appear in CRI. Genetic factors are not excluded. Several studies have demonstrated the existence of genetic abnorm- alities among dialysis patients that lead to lipid metabolism disturbances, such as familial hypercholesterolemia,
1 poly- morphism of the apolipoprotein (apo) AI-CII-AIV gene cluster
2 and paraoxonase (PON) polymorphism.
3 However, it is not yet well established how these factors contribute to the development of accelerated atherosclerosis in dialysis patients. Thus, the interactions between these factors need to
be investigated. The genetic polymorphism of apolipoprotein E (apoE) has been reported by several studies to be involved in lipid metabolism abnormalities and in several metabolic diseases, such as Alzheimer disease and cataracts, in the general population.
4ApoE is a plasma protein that serves as a ligand for low-density lipoprotein (LDL) receptors and is synthesized in various organs, including the liver, brain, spleen and kidney. This protein is present at high concentra- tions in interstitial fluid, where it appears to participate in the cholesterol distribution among cells by transferring excess cholesterol to those cells that require cholesterol. ApoE also appears to be involved in the repair response to tissue injury;
for example, markedly increased levels of apoE are found at sites of peripheral nerve injury and regeneration. Other functions of apoE that are unrelated to lipid transport have been investigated, and these include immunoregulation and the modulation of cell growth and differentiation. The gene encoding this apo has been found to exhibit a polymorphism that results in six phenotypes, namely E2/E2, E2/E3, E2/E4, E3/E3, E3/E4 and E4/E4 from the three co-dominant alleles e2, e3 and e4.
5 Several studies have demonstrated a Address correspondence to Dr. Hanaaˆ Lahrach, Faculty of Sciences
Ben M’sik, Laboratory of Biology and Health, Research Unit Associated to CNRST—URAC 34, Hassan II University, B.P. 7955 Sidi Othmane, Casablanca, Morocco. Tel: + 212 665 378 625; E-mail:
lahrachhanaa@yahoo.fr
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