Hypocholesterolemia and Increased Plasma 7-ketocholesterol Levels in Pediatric Sickle Cell Patients

Abstract

Introduction: Hypocholesterolemia is the most documented lipid abnormality in sickle cell disease  which is also characterized by increased oxidative stress. We investigated plasma levels of oxysterols, oxidized cholesterol derivatives, in the plasma of sickle cell disease patients and compared with controls.

Material and Methods: Twenty steady state sickle cell disease  patients and 8 healthy controls were enrolled in the study. 7-ketocholesterol and cholestane-3β,5α,6β-triol levels, were measured by an LC-MS/MS method. Total cholesterol levels were determined by enzymatic colorimetric method.

Results: Mean plasma total cholesterol levels were significantly lower (109.0±17.4 mg/dl versus 149.6±28.8 mg/dl) (p=0.002) and 7-ketocholesterol levels were higher (10.6±1.9 mg/dl versus 9.0 ±1.2 mg/dl) (p=0.033) in the sickle cell disease  group versus control group. When patients were grouped according to their genotype, Sβ patients (N=10) had higher cholestane-3β,5α,6β-triol levels (p=0.033).

Discussion: To our knowledge this is the first study investigating plasma oxysterols, particularly 7-ketocholesterol and cholestane-3β,5α,6β-triol in sickle cell disease . We found a significant increase in mean 7-ketocholesterol levels in sickle cell disease  patients compared to controls. Patients also had hypocholesterolemia that is typical in many sickle cell disease  patients. Apart from being an oxidative stress marker, 7-ketocholesterol may be a modifier of plasma cholesterol concentration. The metabolic roles of cholesterol oxidation products in diseases warrant further research to explain the tremendous nuclear effects of these oxysterols.

Key words: Oxysterol, 7-ketocholesterol, cholesterol, hypocholesterolemia, oxidative stress