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 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 (Ralpha, Rbeta). To investigate the possible contribution of molecular variants in the human PDGF-A and PDGF-Ralpha 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 gneotyped for newly identified polymorphisms in the genes encoding PDGF-A (C-26IN3T, H69H, C+12IN5T) and PDGF-Ralpha [-1630 I/D (+/-AACTT), A-1506G, C-1390G, G-956A, C-908A, G-793T, +69 I/D (+/-GA)] using allele-specific oligonucleotides. All PDGF-Ralpha 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-Ralpha polymorphisms provided a heterozygosity of 0.69 and 0.40, respectively. Genotype and allele frequencies of the PDGF-A and PDGF-Ralpha 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.
Herrmann
S M
SM
Institut National de la Santé et de la Recherche Médicale (Inserm) SC7/U525, Génétique épidémiologique et Moléculaire des pathologies cardiovasculaires, Paris, France. herrmann@medizin.fu-berlin.de
Ricard
S
S
Nicaud
V
V
Brand
E
E
Behague
I
I
Blanc
H
H
Ruidavets
J B
JB
Evans
A
A
Arveiler
D
D
Luc
G
G
Poirier
O
O
Cambien
F
F
D000328:Adult; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D017422:Sequence Analysis, DNA
D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha