Malondialdehyde (MDA) and protein carbonyl (PCO) levels as biomarkers of oxidative stress in subjects with familial hypercholesterolemia Ayfer Gözü Pirinccioglu a, ⁎, Deniz Gökalp b , Mihdiye Pirinccioglu c , Göksel Kizil c , Murat Kizil c a Department of Pediatrics, Faculty of Medicine, University of Dicle, 21280, Diyarbakir, Turkey b Department of Endocrinology, Faculty of Medicine, University of Dicle, 21280, Diyarbakir, Turkey c Department of Chemistry, Faculty of Science, University of Dicle, 21280, Diyarbakir, Turkey abstract article info Article history: Received 30 April 2010 Received in revised form 16 July 2010 Accepted 17 July 2010 Available online 4 August 2010 Keywords: Hypercholesterolemia Familial Oxidative stress Lipid peroxidation Malondialdehyde Protein carbonylation Atherosclerosis Objective: Familial hypercholesterolemia (FH) is clinically characterized by elevated total and low- density lipoprotein (LDL) cholesterol levels in plasma, which has high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis. The study aims to evaluate oxidative stress in patients with hypercholesterolemia by measuring lipid peroxidation and protein carbonyl (PCO) levels in these patients. PCO in these patients may provide a new diagnostic biomarker for oxidative damage in atherosclerosis. Design and method: Total cholesterol (Tc), low-density lipoprotein-cholesterol (LDL-c), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), lipoprotein(a) (Lp-a) levels and carotid intima-media thickness were measured to evaluate characteristics of patients (11 homozygous and 25 heterozygous) with FH. 25 age–gender–BMI matched healthy control subjects were included in the study for comparison. Results: MDA and PCO levels were significantly higher in homozygous patients compared with those of heterozygous and controls and it was found that they are positively correlated with LDL-c, Tc, Lp-a and IMT while negatively correlated with HDL-c. The heterozygous group also had significantly higher MDA and PCO levels compared with controls. Conclusion: The data obtained could be important for understanding the alterations presented by FH and could be related to their increased risk of developing atherosclerosis. To our knowledge, measurements of PCO in patients with FH are not recorded before and this may be used as a biomarker for protein oxidation, which may play a role in the increased cardiovascular risk of patients with FH. © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Introduction Familial hypercholesterolemia (FH), an autosomal dominant disorder characterized by defects in the low density lipoprotein (LDL) receptor, is associated with a markedly increased risk of developing premature coronary heart disease [1,2]. There are two forms of FH, heterozygous and homozygous. The prevalence of the heterozygous FH is about 1/500 in the general population whereas the homozygous FH is very rare and found about 1 in 1 million people characterized by markedly increased low-density lipoprotein-choles- terol (LDL-c) levels and early onset of atherosclerosis [3,4]. The genetic basis of FH is the lack of functional receptors for LDL on the cell surface in liver and peripheral tissue [3]. As a result, plasma LDL concentrations are elevated and its plasma half-life prolonged, possibly leading to increased susceptibility to free radical attack and oxidation. Endothelial cells, smooth muscle cells, neutrophils and monocytes all have the potential to oxidatively modify LDL, leading to the generation of lipid peroxidation products and reactive oxygen species, which is responsible for oxidative stress involved in degenerative disease, including atherosclerosis [5,6]. This can be measured by monitoring the changes in blood malondialdehyde (MDA) and carbonyl content. Determination of carbonyl level is used as an index of the extent of the oxidative damage of protein while malondialdehyde level is a marker of lipid oxidation. Antioxidants work together in human blood cells against toxic reactive oxygen species [7–9]. Reactive oxygen species (ROS) cause lipid peroxidation and oxidation of some specific proteins, thus affecting many intra- and intercellular systems [10]. Some ROS- induced protein modifications can result in unfolding or alteration of protein structure, and some are essentially harmless events. Irrevers- ible protein modifications can lead to inactivation of various proteins and could have lasting detrimental cellular effects [11]. Many different types of protein oxidative modification can be induced by ROS. Carbonylation is an irreversible, non-enzymatic modification of proteins. Carbonyl groups are introduced into proteins by a variety of oxidative pathways. ROS can react directly with the protein or they can react with molecules such as sugars and lipids, generating products (reactive carbonyl species) that then react with protein and Clinical Biochemistry 43 (2010) 1220–1224 ⁎ Corresponding author. E-mail addresses: ayfergozu@dicle.edu.tr, ayfergozu@hotmail.com (A.G. Pirinccioglu). 0009-9120/$ – see front matter © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.clinbiochem.2010.07.022 Contents lists available at ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem