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Polymorphisms in the genes encoding platelet-derived growth factor A and alpha receptor
S M Herrmann1, S Ricard, V Nicaud
1Institut 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
Insights
Genetic variations in Platelet-Derived Growth Factor A (PDGF-A) and PDGF Receptor Alpha (PDGF-Ralpha) genes were not associated with myocardial infarction risk in European populations. This study found no link between these specific gene polymorphisms and coronary heart disease development.
Area of Science:
- Genetics
- Cardiovascular Disease Research
- Molecular Biology
Background:
- Platelet-Derived Growth Factors (PDGFs) are implicated in atherosclerosis development, influencing vascular smooth muscle cells and macrophages.
- Distinct PDGF (AA, AB, BB) forms and their receptors (PDGF-Ralpha, PDGF-Rbeta) exhibit varied activities.
- Investigating genetic variants in PDGF-A and PDGF-Ralpha is crucial for understanding coronary heart disease (CHD) etiology.
Purpose of the Study:
- To screen for polymorphisms in human PDGF-A and PDGF-Ralpha genes.
- To determine if identified gene variants contribute to the risk of myocardial infarction (MI).
- To analyze the association of these polymorphisms with cardiovascular risk factors.
Main Methods:
- Polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) analysis was used to identify polymorphisms.
- Genotyping of PDGF-A and PDGF-Ralpha polymorphisms was performed in 600 MI patients and 717 controls (ECTIM Study).
- Allele-specific oligonucleotides were employed for genotyping various identified polymorphisms.
Main Results:
- No significant differences in genotype or allele frequencies of PDGF-A and PDGF-Ralpha polymorphisms were observed between MI patients and controls.
- The identified PDGF-A and PDGF-Ralpha polymorphisms showed heterozygosity of 0.69 and 0.40, respectively.
- None of the investigated polymorphisms were associated with blood pressure, coronary artery stenosis, or biochemical parameters.
Conclusions:
- The studied polymorphisms in the PDGF-A and PDGF-Ralpha genes do not appear to be risk factors for myocardial infarction in the examined European populations.
- Further research may be needed to explore other genetic factors influencing coronary heart disease.
- The findings suggest that variations in PDGF-A and PDGF-Ralpha are unlikely to be major contributors to CHD susceptibility.
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 (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.