Analysis on the relevance of asthma susceptibility with the alteration of integrin β 4 expression.

Abstract

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 β4, which was down-regulated in all asthma patients, to analyze the relevance of asthma susceptibility with the alteration of integrin β4 expressions. Real time PCR was used to verify the down-regulation of integrin β4 in additional 38 asthma patients. Next, the 5'flanking region of integrin β4 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 β4, 3 were related to asthma susceptibility: -nt1029 G/A, -nt 1051 G/A, and -nt 1164 G/C. A reduction of human integrin β4 promoter activity was observed at mutants of these sites. This study demonstrates that various adhesion molecules in asthma patients are abnormally expressed. Mutations in 5' flanking region result in reduced integrin β4 expression, which is related to increased risk of asthma.