Summary:
This study investigates 3 common polymorphisms (R219K, R1587K and I883M) in
ABCA1 gene in healthy young individuals. These polymorphisms are related with
lipids levels. This association of common polymorphisms, indicates the
important role of ABCA1 protein in lipid metabolism.
Tangier disease (TD) is a phenotypic expression of rare familial syndrome with
mutations in ABCA1 gene, which can cause absence or less activity of ABCA1
protein and these patients have a characteristic lipid profile. High density
lipoprotein (HDL) which has a protective role, in TD patients is very low or is
almost absent. However, the risk of coronary artery disease (CAD) in patients
with TD is variable, because the progress of CAD depends from many mechanisms,
the most of them are not very clear, yet. Moreover, CAD which is a chronic
disease is related with inflammation.
The pivotal role of Platelet-Activating Factor (PAF) mediator in atheromatosis
is found. Plasma lipoproteins are transporters of the platelet activating
factor acetylhydrolase (PAF-AH) also known as lipoprotein-phospholipase A2
(Lp-PLA2) and regulate PAF levels in blood. PAF biosynthesis depends on the
remodeling and the de novo pathways in which lyso-PAF-acetyltransferase
(Lyso-PAF-AT) and PAF-cholinephosphotrans-ferase (PAF-CPT) are the regulatory
enzymes, respectively.
Another aim of this study is to investigate in a TD patient with a unique
mutation (C2033A), the concentration of PAF in blood, the Equivalent
Concentration for 50% aggregation (EC50) values of platelet rich plasma (PRP)
toward PAF, ADP and thrombin, and the specific activities of PAF metabolic
enzymes Lp-PLA2, PAH-AH, Lyso-PAF-AT and PAF-CPT.
Keywords:
Tangier disease, Αtherosclerosis, Polymorphism, Mutation, PAF metabolism
