title: DNA sequence variants of the platelet-derived growth factor A-chain gene.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: R
authors.initials: R
authors.lastname: Baron
authors.forename: E S
authors.initials: ES
authors.lastname: Silverman
authors.forename: H
authors.initials: H
authors.lastname: Grasemann
authors.forename: T
authors.initials: T
authors.lastname: Collins
authors.forename: J M
authors.initials: JM
authors.lastname: Drazen
mesh_terms: D001249:Asthma / Q000235:genetics; D001483:Base Sequence / Q000235:genetics*; D044383:Black People / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005815:Genetic Code / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D012313:RNA