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

Penelope E. Graves, Michael Kabesch, Marilyn Halonen, Catharine J. Holberg, Mauro Baldini, Christian Fritzsch, Stephan K. Weiland, Robert P. Erickson, Erika Von Mutius, Fernando D. Martinez

Research output: Contribution to journalArticlepeer-review

356 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)506-513
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume105
Issue number3
DOIs
StatePublished - 2000

Keywords

  • Asthma
  • IL-13
  • IgE
  • Polymorphisms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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