STUDY OF APOLIPOPROTEIN E POLYMORPHISM AS A GENETIC BIOMARKER IN CORONARY ARTERY DISEASES

Abstract

The plasma lipoproteins arc complex macromolecular structures which play an essential role in l 1t transport and in energy and membrane metabolism of higher organized organisms; their protein moieties, the so-called apolipoprotcins (Middclhoft: eta/., 1977).

Apolipoprotcin E is a member of apolipoprotein gene t unily. Apo E gene located on chromosome 19q 13.2 and is closely linked to Apo C-II Apo C-II gene complex. It consists of four exons and three introns spanning 3,597 nucleotides and produces a 299 amino acid polypeptide. It is synthesized primarily in the liver, but other organs and tissues also synthesize apo E including brain, spleen, kidneys, gonads, adrenals, and macrophages. The structural gene is polymorphic with three common alleles, e2, e3 and e4 producing three isoforms of the protein E2. E3 and E4. These isoforms differ in amino acid sequence at position 112 and 158 .Apo E3 consists cysteine at 112 and arginine in 158. Apo E2 has cysteine at both position, and E4 has arginine at both sites .Polymorphism with its three alleles has been studied in relation to cardiovascular disease (June, eta/., 2002). The protein is involved in the efficient hepatic uptake of lipoprotein particles, stimulation of cholesterol efflux from macrophage foam cells in the atherosclerotic lesion, and the regulation of immune and inflammatory responses (Kirst)', eta/., 2005). Also, Apolipoprotein E plays a key role in the metabolism of cholesterol and triglycerides

(Mahley and Rail, 2000).