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 metaboli sm by binding to lipoprotein lipase (LpL) and apolipoprotein B (apo B) and may be related to vascular disease. We explored interactions between an HSP G2 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, wi th a '+' allele frequency of 20.6%. The genotype distribution was in Hardy- Weinberg equilibrium (chi(2) = 0.669, P > 0.05). The +/+ homozygotes had th e 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/I, n=480) genotypes. Although plasma apo B concentration was the strangest lipid risk factor Far significant CA D, 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 a rteries (P=0.945; P=0.335). In Australian Caucasians undergoing coronary an giography 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 H SPG2-mediated alterations in the HSPG2-apo B-LpL system and requires furthe r exploration. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.