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

Abstract.

Platelet-derived growth factors (PDGFs) may play an important role in the development of atherosclerosis acting as chemoattractants and mitogens for vascular smooth muscle cells and macrophages. Three dimeric forms of PDGF (AA, AB, BB) have different activities due to distinct binding properties mediated by two types of PDGF receptors (Rα, Rβ). To investigate the possible contribution of molecular variants in the human PDGF-A and PDGF-Rα genes to coronary heart disease we screened these genes for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism analysis. A total of 600 men with myocardial infarction and 717 age-matched male controls from four populations in Northern Ireland and France (the ECTIM Study) were genotyped for newly identified polymorphisms in the genes encoding PDGF-A (C–26IN3T, H69H, C+12IN5T) and PDGF-Rα [–1630 I/D (+/–AACTT), A–1506G, C–1390G, G–956A, C–908A, G–793T, +69 I/D (+/–GA)] using allele-specific oligonucleotides. All PDGF-Rα polymorphisms, except C–908A, involving a nucleotide change in a common consensus site for GCF and SP-1 transcription factors, were in nearly complete association, generating two major haplotypes. The PDGF-A and PDGF-Rα polymorphisms provided a heterozygosity of 0.69 and 0.40, respectively. Genotype and allele frequencies of the PDGF-A and PDGF-Rα polymorphisms did not differ between patients with myocardial infarction and controls in either country. None of the polymorphisms investigated was associated with blood pressure, coronary artery stenosis, or any biochemical parameter available in the ECTIM Study.