A Diagnostic Biomarker for Human Fish Eye Disease: A Systems Biology Approach for Lipid Metabolism Disorders

Fish eye disease is caused by mutations in the gene coding for the Lecithin cholesterol acyltransferase (LCAT) protein. This enzyme is responsible for the conversion of cholesterol to cholesteryl-ester in HDL and LDL with the α- and β-activity of LCAT respectively.Furthermore, Apo AI is considered as an activator of LCAT. The protein is expressed in the liver and secreted into plasma. Based on literature, all protein expressions on HDL is almost at the level of baseline in people with LCAT deficiency.Aim: To find a prognostic biomarker for Fish Eye Disease Method: Blood samples were drawn in tube coated with anti-coagulants, spun and plasma collected. Subsequently, the Plasma lipoproteins (VLDL, LDL and HDL) were collected based on salt gradient centrifugation. Systems Biology was applied to discover proteins present on VLDL, LDL and HDL fractions and to discover the biomarker candidatesResults and conclusion: The differences in gel electrophoresis (DIGE) in combination with tandem MS shows a shifting of a specific protein from VLDL to HDL. The expression of this protein was highest on HDL as compared to other two plasma lipoproteins. A combination of Biochemistry, DIGE and NLC-MS-MS proved to be a powerful tool discovery of biomarkers in cardiovascular diseases and lipid metabolism disorders.