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.
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.


CONCLUSIONS
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.
Sandford
A J
AJ
UBC McDonald Research Laboratories, St Paul's Hospital, and the Respiratory Division, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Zhu
S
S
Bai
T R
TR
Fitzgerald
J M
JM
Paré
P D
PD
D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology
D018946:Chemokine CCL5; D019713:Receptors, CCR5