Background Platelet-derived growth factor A-chain (PDGF-A) is a potent connective tissue mitogen implicated in lung growth and development. PDGF-A may have a role in asthma through effects on fibroblasts and bronchial smooth muscle cells.
Objective To test the hypothesis that there exist variations in the PDGF-A gene associated with the asthma phenotype.
Methods We screened genomic DNA from normal and asthmatic subjects using single-stranded conformational polymorphism (SSCP) for mutations in the promoter and all seven exons of the gene.
Results Four transition polymorphisms (three novel) were identified: one each in exons 3 and 4 (overall population allele frequencies 0.18 and 0.02, respectively) which did not alter the protein sequence, one in exon 4 (frequency 0.005) which resulted in a valine to isoleucine substitution, and one in intron 5 (frequency 0.5). The intron 5-sequence variant is close to the 3′ end of exon 5 but does not appear to affect alternative splicing of PDGF-A exon 6 RNA. The frequencies of the polymorphisms in exons 3 and intron 5 did not differ between the asthmatic and non-asthmatic subjects, but there was a significant frequency difference between Caucasian and African-American subjects for each of these polymorphisms (P = 0.03 and 0.003, respectively).
Conclusion No association was found between the sequence variants in the PDGF-A gene and the development of asthma. However, the allele frequency of some of the sequence variants differed between the Caucasian and African-American subjects.