Genetic polymorphism of heparan sulfate proteoglycan (perlecan, HSPG2), lipid profiles and coronary artery disease in the Australian population.
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.
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Cardiovascular Genetics Laboratory, Ground Floor, South Wing, Edmund Blacket Building, Prince of Wales Hospital, Randwick, Sydney, Australia.
Wang
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Wilcken
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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
D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008055:Lipids; D020033:Protein Isoforms; D011509:Proteoglycans; C071927:perlecan