A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children
| Autor: | Fernando D. Martinez, Mauro Baldini, Robert P. Erickson, Erika von Mutius, Stephan K. Weiland, Penelope E. Graves, Marilyn Halonen, Christian Fritzsch, Michael Kabesch, Catharine J. Holberg |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Genotype
Immunology Immunoglobulin E Polymorphism (computer science) Respiratory Hypersensitivity Humans Multicenter Studies as Topic Immunology and Allergy Coding region Child Gene Skin Tests Genetics Interleukin-13 Polymorphism Genetic biology Promoter Asthma Restriction site Cross-Sectional Studies Child Preschool Interleukin 13 biology.protein |
| Zdroj: | Journal of Allergy and Clinical Immunology. 105:506-513 |
| ISSN: | 0091-6749 |
| DOI: | 10.1067/mai.2000.104940 |
| Popis: | Background: Increased levels of total serum IgE are a strong risk factor for the development of asthma. IgE is also involved in host defenses against parasites and fungi. Linkage of total serum IgE with markers located close to the 3 Mb cluster of cytokine genes in chromosome 5q31 has been reported. IL-4 or IL-13 are regarded as essential for IgE synthesis. Objective: We tested whether polymorphisms in the IL-13 gene might explain the linkage between chromosome 5q31 and total serum IgE levels. Methods: We used denaturing HPLC to detect polymorphisms in overlapping PCR fragments of the IL-13 gene including promoter and 3′ untranslated regions. After sequencing was performed to identify the locations of the polymorphisms, PCR and primer-induced restriction site assays were used to genotype subjects in 3 unselected populations. Results: We report here 7 polymorphisms (6 novel) in IL-13. Four of these polymorphisms are tightly linked to a variant in the terminal portion of the coding region of the gene that results in a predicted amino acid change in residue 130 (Arg130Gln). The Gln form is strongly associated ( P = .000002) with increased serum IgE levels in 3 different populations comprising a total of 1399 children. Two additional polymorphisms in the promoter region of IL-13 are more loosely linked to Arg130Gln and are also less significantly associated with total serum IgE levels. Conclusion: These data suggest that the Arg130Gln polymorphism in IL-13, or others in close linkage with it, is associated with the development of the elevated serum IgE phenotype. (J Allergy Clin Immunol 2000;105:506-13.) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect