Coronary artery disease, lipid disorders and genetic polymorphisms.
Coronary artery disease (CAD) is the leading cause of morbidity and mortality in most industrialized countries, accounting for one out of every two deaths in the United States. Disorders of the lipid transport system resulting from complex interactions among nutritional, environmental and genetic factors, play a very important role in the development of this disease. It has been proposed that low density lipoproteins (LDL) cause cholesterol deposition in the arterial wall, whereas high density lipoproteins (HDL) promote efflux of cholesterol from this site. Thus, low levels of HDL and/or high levels of LDL, have been associated with increased risk of CAD. Apolipoprotein A-I (Apo A-I) is the major protein component of HDL, and it has been proposed that the levels of this protein are a better predictor of risk of CAD than the level of cholesterol in HDL. The human Apo A-I gene has been characterized, and it has been found to be adjacent to the genes for apolipoproteins C-lll and A-lV on the long arm of chromosome 11. The cloning of these genes provides the appropriate tools to apply molecular genetic techniques to find differences between individuals at the gene level (restriction fragment length polymorphisms, RFLP) and to identify specific alleles at this particular gene locus which may be associated with a clinical phenotype, more specifically, premature CAD and familial hypoalphalipoproteinemia. In a preliminary study we have identified a Pst I restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic.(ABSTRACT TRUNCATED AT 250 WORDS)
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008074:Lipoproteins; D004247:DNA