DNA sequence variants of the platelet-derived growth factor A-chain gene.
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.
Baron
R
R
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Silverman
E S
ES
Grasemann
H
H
Collins
T
T
Drazen
J M
JM
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
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D012313:RNA