Increased plasma 7-ketocholesterol levels may explain the hypocholesterolemia of sickle cell disease patients

Yalçinkaya A., Samadi A., Lay I., Ünal S., Er Öztaş Y.

Febs Journal, vol.283, pp.64, 2017 (SCI-Expanded)

  • Publication Type: Article / Abstract
  • Volume: 283
  • Publication Date: 2017
  • Journal Name: Febs Journal
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.64
  • Hacettepe University Affiliated: Yes


INTRODUCTION Sickle cell disease (SCD) occurs due to a point mutation in the hemoglobin gene. It is characterized by anemia, vasooclusion and chronic inflammation. Hypocholesterolemia is a common finding in SCD patients; however, there are only a few studies to explain its etiology. We had previously shown that SCD patients had a negative correlation between their plasma cholesterol and erythrocyte malonyldialdehyde levels. We hypothesized that increased cholesterol oxidation may be a factor for hypocholesterolemia in SCD. MATERIAL AND METHODS The study consisted of pediatric SCD patients (N=22) and healthy controls (N=8). The patients hadn’t had any crisis for the last three months except two. Blood samples were drawn into EDTA tubes to separate plasma. Levels of holesterol oxidation products,  7-ketocholesterol and Colestane-3β,5α,6β-triol were measured by LCMS/MS with the method by Griffiths et al. Plasma total cholesterol levels were measured by commercial kits. Statistical analysis was performed with Graphpad Prism 6.0 This study was approved by the Institutional Review Board of Mersin University. FINDINGS Mean 7-ketocholesterol levels were 10.47±1.83 ng/ml in patients and 8.97±1.05 ng/ml in controls (P=0.0298). Mean Colestane-3β,5α,6β-triol levels were 6.49±2.31 in patients and 5.69±2.69 in controls (P=0.4283). Mean Cholesterol levels were 106±19.1 mg/dL in patients and 149.6±28.9 in controls (P<0.0001). DISCUSSION We found significantly lower plasma cholesterol and higher 7-ketocholesterol levels in SCD patients than controls. We suggest that increased oxidative stress should be considered as a factor contributing to hypocholesterolemia in SCD besides hemolysis and inflammation suggested by two previous studies. This is the first report investigating plasma oxysterol levels in SCD patients in literature. Further studies are needed to understand the effects of hypocholesterolemia and increased cholesterol oxidation products in SCD.