Polymorphisms in the genes encoding platelet-derived growth factor A and alpha receptor

Platelet-derived growth factors (PDGFs) may play an important role in the d evelopment of atherosclerosis acting as chemoattractants and mitogens for v ascular smooth muscle cells and macrophages. Three dimeric forms of PDGF (A A, AB, BB) have different activities due to distinct binding properties med iated by two types of PDGF receptors (R alpha, R beta). To investigate the possible contribution of molecular variants in the human PDGF-A and PDGF-R alpha genes to coronary heart disease we screened these genes for polymorph isms by polymerase chain reaction/single-strand conformation polymorphism a nalysis. A total of 600 men with myocardial infarction and 717 age-matched male controls from four populations in Northern Ireland and France (the ECT IM Study) were genotyped for newly identified polymorphisms in the genes en coding PDGF-A (C-26IN3T, H69H, C+12IN5T) and PDGF-R alpha [-1630 I/D (+/-AA CTT), A-1506G, C-1390G, G-956A, C-908A, G-793T, +69 I/D (+/-GA)] using alle le-specific oligonucleotides. All PDGF-R alpha polymorphisms, except C-908A , involving a nucleotide change in a common consensus site for GCF and SP-I transcription factors, were in nearly complete association, generating two major haplotypes. The PDGF-A and PDGF-R alpha polymorphisms provided a het erozygosity of 0.69 and 0.40, respectively. Genotype and allele frequencies of the PDGF-A and PDGF-R alpha polymorphisms did not differ between patien ts with myocardial infarction and controls in either country. None of the p olymorphisms investigated was associated with blood pressure, coronary arte ry stenosis, or any biochemical parameter available in the ECTIM Study.