2000年3月
Genetic variants of IL-13 signalling and human asthma and atopy
HUMAN MOLECULAR GENETICS
- 巻
- 9
- 号
- 4
- 開始ページ
- 549
- 終了ページ
- 559
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/hmg/9.4.549
- 出版者・発行元
- OXFORD UNIV PRESS
Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4R alpha and either gamma c or IL-13R alpha 1) and IL-13 operates through IL-13R (a heterodimer of IL-4R alpha and IL-13R alpha 1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy. Recent animal model data suggest that IL-13 is a central cytokine-in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity. We investigated the role of common genetic variants of IL-13 and IL-13R alpha 1 in human asthma, considering IgE levels. A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 2.31, 95% CI 1.33-4.00]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population. Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects. Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gin, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction. A non-coding variant of IL-13R alpha 1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3.38 in males, 1.10 in females) rather than asthma. Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed.
- リンク情報
- ID情報
-
- DOI : 10.1093/hmg/9.4.549
- ISSN : 0964-6906
- eISSN : 1460-2083
- PubMed ID : 10699178
- Web of Science ID : WOS:000085781000010