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

被引:56
作者
DeMeo, DL
Lange, C
Silverman, EK
Senter, JM
Drazen, JM
Barth, MJ
Laird, N
Weiss, ST
机构
[1] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA
关键词
interleukin; 13; single-nucleotide polymorphism; eosinophils; allergy; asthma; family-based; genetic association studies;
D O I
10.1002/gepi.10182
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 FBATGEE, 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. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:335 / 348
页数:14
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