Analysis on the Relevance of Asthma Susceptibility with the Alteration of Integrin β 4 Expression

Accumulated research has suggested the importance of the adhesion molecules modulation as therapeutic approach for bronchial asthma. Adhesion molecules expression alteration contributes to the pathogenesis of asthma. In order to probe the roles of expression imbalance of adhesion molecules in asthma pathogenesis, expression profiling of adhesion molecules was performed using cDNA microarray assay. The results showed that the expression pattern of adhesion molecules was altered in peripheral blood leucocytes of asthma patients. In this study, we focused on one of the abnormally expressed molecule, integrin beta 4, which was down-regulated in all asthma patients, to analyze the relevance of asthma susceptibility with the alteration of integrin beta 4 expressions. Real time PCR was used to verify the down-regulation of integrin beta 4 in additional 38 asthma patients. Next, the 5'flanking region of integrin beta 4 DNA were amplified, sequenced and site-directed mutagenesis technology in correspondent variation sites were carried out. Among 4 variation sites found in 5' flanking region of integrin beta 4, 3 were related to asthma susceptibility: -nt1029 G/A, -nt 1051 G/A, and -nt 1164 G/C. A reduction of human integrin beta 4 promoter activity was observed at mutants of these sites. This study demonstrates that various adhesion molecules in asthma patients are abnormally expressed. Mutations in 59 flanking region result in reduced integrin beta 4 expression, which is related to increased risk of asthma.