DNA sequence variants of the platelet-derived growth factor A-chain gene

• Published in: Clinical and experimental allergy Vol. 31; no. 10; pp. 1501 - 1508
• Main Authors: Baron, R., Silverman, E. S., Grasemann, H., Collins, T., Drazen, J. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.10.2001; Blackwell; Wiley Subscription Services, Inc
• Subjects: airway remodelling; Allergic diseases; asthma; Asthma - genetics; Base Sequence - genetics; Biological and medical sciences; Black or African American; Black People - genetics; Gene Frequency - genetics; Genetic Code - genetics; Genetic Variation - genetics; Humans; Immunopathology; Medical sciences; mutation; PDGF-A gene; platelet-derived growth factor; Platelet-Derived Growth Factor - genetics; platelet-derived growth factor A-chain; Point Mutation - genetics; Polymerase Chain Reaction; polymorphism; Polymorphism, Single Nucleotide - genetics; Polymorphism, Single-Stranded Conformational; Respiratory and ent allergic diseases; RNA - genetics; RNA, Messenger - genetics; Sequence Analysis, DNA; single-stranded conformational polymorphism analysis; White People - genetics; Human; Respiratory disease; Single stranded DNA; Remodeling; Genetic determinism; Single strand conformation polymorphism; Asthma; Respiratory tract; Gene; Obstructive pulmonary disease; Platelet derived growth factor; Growth factor; Polymorphism
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.2001.01197.x

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.