Univariate and multivariate family‐based association analysis of the IL‐13 ARG130GLN polymorphism in the Childhood Asthma Management program

Abstract

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. Genet. Epidemiol. 23:335–348, 2002.