Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 70, Issue 1, Pages 230-236Publisher
UNIV CHICAGO PRESS
DOI: 10.1086/338242
Keywords
-
Categories
Funding
- 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
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available