期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 70, 期 1, 页码 230-236出版社
UNIV CHICAGO PRESS
DOI: 10.1086/338242
关键词
-
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL066393, R01HL048341] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL048341, R01HL/66393, R01 HL066393, R01HL/48341] Funding Source: Medline
Asthma is a common respiratory disease that is characterized by variable airways obstruction caused by acute and chronic bronchial inflammation; associated phenotypes include bronchial hyperresponsiveness (BHR), elevated total serum immunoglobulin E (IgE) levels, and skin tests positive to common allergens. Binding of interleukin-13 (IL13) or interleukin-4 (IL4) to the IL4 receptor (IL4R) induces the initial response for Th2 lymphocyte polarization. Both IL13 and IL4 are produced by Th2 cells and are capable of inducing isotype class-switching of B-cells to produce IgE after allergen exposure. These cytokines also share a common receptor component, IL4R. We have investigated five IL4RA single-nucleotide polymorphisms in a population of Dutch families ascertained through a proband with asthma. By considering the probands and their spouses as an unrelated sample, we observed significant associations of atopy and asthma-related phenotypes with several IL4RA polymorphisms, including S478P and total serum IgE levels (P=.0007). A significant gene-gene interaction between S478P in IL4RA and the - 1111 promoter variation in IL13, previously shown to be associated with BHR (P = .003), was detected. Individuals with the risk genotype for both genes were at almost five times greater risk for the development of asthma compared to individuals with both nonrisk genotypes (P = .0004). These data suggest that variations in IL4RA contribute to elevated total serum IgE levels, and interaction between IL4RA and IL13 markedly increases an individual's susceptibility to asthma.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据