Apolipoprotein H (APOH) is an essential cofactor for the binding of antiphospholipid antibodies to anionic phospholipids, suggesting that structural variations in the APOH molecule may have a significant impact on the binding of autoantibodies to their substrate; thus, determining the outcome of thrombosis. Based upon the current physiologic role of APOH and the information that the APOH gene is genetically polymorphic, the investigators hypothesize that genetically determined structural changes in the phospholipid interaction binding sites on the APOH molecule have a significant impact in determining the binding affinity of antiphospholipid autoantibodies and the occurrence of associated thrombotic events in patients with systemic lupus erythematosus (SLE). The proposed comprehensive study will establish the molecular basis of known structural and quantitative polymorphism by direct sequencing of the expressed portion of the APOH gene (Aim 1); detect new and common genetic polymorphisms in the APOH gene (Aim 2); perform in vitro expression studies and examine the binding abilities of various APOH allele products to anionic phospholipids (Aim 3); compare the quantitative plasma levels of APOH between SLE patients and controls (Aim 4); evaluate the relationship between APOH polymorphisms and quantitative plasma levels of APOH (Aim 5); determine the frequency distributions of known APOH polymorphisms in SLE patients and controls (Aim 6); and evaluate the relationship between genetically defined structural polymorphisms, and quantitative polymorphism in the APOH gene, and the occurrence of antiphospholipid antibodies in SLE patients (Aim 7). The investigators state that the proposed studies will facilitate the identification and characterization of the role of APOH genetic polymorphisms in the prediction of the antiphospholipid antibodies in SLE patients.
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