Eotaxin polymorphisms and serum total IgE levels in children with asthma.
BACKGROUND
Eotaxin (chemokine, CC motif, ligand; CCL11) is a potent eosinophil chemoattractant strongly implicated in the pathobiology of asthma. Genetic variation at the CCL11 locus has been correlated with serum total IgE, blood eosinophil counts, and circulating eotaxin protein levels in several case-control asthma studies. Family-based association studies of CCL11 genetic variants have not been reported to date.


OBJECTIVE
To evaluate 9 common CCL11 single nucleotide polymorphisms (SNPs) in nuclear families ascertained through patients with asthma participating in the Childhood Asthma Management Program study.


METHODS
Single nucleotide polymorphism genotyping was performed by using minisequencing and probe hybridization platforms. Family-based association analysis for asthma and 4 asthma-related intermediate quantitative phenotypes was performed by using FBAT.


RESULTS
One SNP, -384A>G, was associated with asthma among African American families (P = .01). CCL11 SNPs and haplotypes were not associated with asthma among white or Hispanic families. Two low-frequency alleles in strong pairwise linkage disequilibrium, -426C and IVS2+199A, were associated with lower serum total IgE levels (P = .0006 and P = .009, respectively) in white families, whereas 2 more common variants, -576C and g.4438C, were associated with higher IgE levels in African American families (P = .01-.04). Haplotype analysis in the white cohort provided additional evidence of association with serum total IgE, implicating 2 haplotypes. No single SNP or haplotype associations were observed with blood eosinophil levels, FEV(1), or airway responsiveness.


CONCLUSIONS
These findings provide further evidence that genetic variation at the CCL11 locus is an important determinant of serum total IgE levels among patients with asthma.
Raby
Benjamin A
BA
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. benjamin.raby@channing.harvard.edu
Van Steen
Kristel
K
Lazarus
Ross
R
Celedón
Juan C
JC
Silverman
Edwin K
EK
Weiss
Scott T
ST
D000328:Adult; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044383:Black People; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000235:genetics*; D002648:Child; D006630:Hispanic or Latino; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D044465:White People; D001741:Black or African American
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D007073:Immunoglobulin E