The role of the C-C chemokine receptor-5 Delta32 polymorphism in asthma and in the production of regulated on activation, normal T cells expressed and secreted

Abstract

Background: There are conflicting data regarding the role of a deletion in the C-C chemokine receptor-5 gene (CCR5*D32) in the pathogenesis of asthma and whether this deletion influences the production of regulated on activation, normal T cells expressed and secreted (RANTES). RANTES is a chemokine that is known to play an important role in the pathogenesis of allergic asthma.

Objective: We sought to determine whether CCR5*D32 is associated with increased RANTES production, the presence of asthma, and the severity of asthma.

Methods: A PCR assay for CCR5*D32 was developed. The prevalence of CCR5*D32 was determined in a group of patients with mild-to-moderate asthma, a group of subjects with severe asthma who had fatal or near-fatal asthma attacks, and a group of nonasthmatic control subjects. The level of RANTES produced by stimulated and unstimulated T cells was measured by using a commercially available immunoassay.

Results: The frequency of CCR5*D32 was not significantly increased in the severe asthma group compared with in the mild-to-moderate asthma group. CCR5*D32 was not increased in the asthmatic subjects versus in the control subjects. There was no significant increase in RANTES levels from T cells heterozygous for CCR5*D32 compared with wild-type cells.

Conclusion: These data indicate that the CCR5*D32 allele is not a genetic risk factor for the development of asthma and does not influence disease severity. The CCR5*D32 allele does not influence RANTES production in the heterozygous state.