title: Genetic polymorphism of heparan sulfate proteoglycan (perlecan, HSPG2), lipid profiles and coronary artery disease in the Australian population.
abstract: Perlecan is one of the three major classes of heparan sulfate proteoglycans (HSPGs) within the cardiovascular system; it interacts with lipid metabolism by binding to lipoprotein lipase (LpL) and apolipoprotein B (apo B) and may be related to vascular disease. We explored interactions between an HSPG2 polymorphism (BamHI marker), and apo B and coronary artery disease (CAD) in patients undergoing coronary angiography. The frequencies of the HSPG2 BamHI +/+, +/-, and -/- genotypes were 4.7, 31.7 and 63.6%, respectively, with a '+' allele frequency of 20.6%. The genotype distribution was in Hardy-Weinberg equilibrium (chi(2)=0.669, P0.05). The +/+homozygotes had the lowest apo B levels (0.74+/-0.06 g/l, n=36) compared to +/- (0.89+/-0.03 g/l, n=241) and -/- (0.93+/-0.02 g/l, n=480) genotypes. Although plasma apo B concentration was the strongest lipid risk factor for significant CAD, the HSPG2 genotypes were not independently associated with the presence of CAD (P=0.640 in males; P=0.224 in females), with significant CAD (P=0.764; P=0.110) or with the number of significantly stenosed coronary arteries (P=0.945; P=0. 335). In Australian Caucasians undergoing coronary angiography the HSPG2 BamHI polymorphism is associated with lower circulating apo B but not with the occurrence or severity of CAD. This may be due to HSPG2-mediated alterations in the HSPG2-apo B-LpL system and requires further exploration.
authors.affiliation: Cardiovascular Genetics Laboratory, Ground Floor, South Wing, Edmund Blacket Building, Prince of Wales Hospital, Randwick, Sydney, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Cai
authors.forename: X L
authors.initials: XL
authors.lastname: Wang
authors.forename: D E
authors.initials: DE
authors.lastname: Wilcken
mesh_terms: D001315:Australia; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics*; D006497:Heparan Sulfate / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics
chemical_list: D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008055:Lipids; D020033:Protein Isoforms; D011509:Proteoglycans; C071927:perlecan