Univariate and multivariate family-based association analysis of the IL-13 ARG130GLN polymorphism in the Childhood Asthma Management Program.
Interleukin 13 (IL-13) has been demonstrated to have a crucial role in animal models of allergy and asthma. In human case-control genetic-association studies, the Arg130Gln polymorphism has been associated with elevated total serum IgE and an asthma diagnosis in atopic and nonatopic individuals (Graves et al. [2000] J. Allergy Clin. Immunol. 105:506-513; Heinzmann et al. [2000] Hum. Mol. Genet. 9:549-559). To apply family-based association methods, we obtained DNA samples from 685 asthmatic children from 640 sibships and their parents in the Childhood Asthma Management Program (CAMP). Six hundred and sixty-six asthmatic children had complete phenotypic information and were used for this analysis. We performed quantitative association analysis using the transmission disequilibrium test (TDT) on 22 individual phenotypes and 5 grouped phenotypes relating to allergy, airway responsiveness, pulmonary function, bronchodilator responsiveness, and asthma severity, using genotypes at the Arg130Gln polymorphism of the IL-13 gene. A positive association was obtained between Arg130Gln and a grouped phenotype of allergy (consisting of the individual phenotypes of eosinophils, IgE, and positive skin tests), using FBAT-GEE, a multivariate extension of the family-based association test (Lange et al. [2002] Biostatistics 1:1-15). The three phenotypes were then evaluated individually and revealed a significant association between total eosinophil count and the Arg130Gln locus; there was a trend for association between total IgE and the Arg130Gln polymorphism. The Arg130Gln polymorphism is associated with an elevated eosinophil count as well as with a grouped allergy phenotype, in children with mild to moderate asthma. No evidence for association was found between Arg130Gln and airway responsiveness, asthma diagnosis, or asthma severity.
DeMeo
D L
DL
Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Lange
C
C
Silverman
E K
EK
Senter
J M
JM
Drazen
J M
JM
Barth
M J
MJ
Laird
N
N
Weiss
S T
ST
D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016009:Chi-Square Distribution; D002648:Child; D004247:DNA / Q000032:analysis; D004804:Eosinophils; D005260:Female; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics* / Q000276:immunology; D015810:Linkage Disequilibrium; D008297:Male; D009679:Nuclear Family; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests; D012720:Severity of Illness Index
D000485:Allergens; D018793:Interleukin-13; D007073:Immunoglobulin E; D004247:DNA