A complete screening of the IL4 gene: Novel polymorphisms and their association with asthma and IgE in childhood

Michael Kabesch, Iren Tzotcheva, David Carr, Claudia Höfler, Stephan K. Weiland, Christian Fritzsch, Erika Von Mutius, Fernando Martinez

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Background: IL-4, a cytokine with immunomodulatory functions, is involved in the upregulation of IgE production characteristic of asthma and allergy. Thus far, 2 single nucleotide polymorphisms (SNPs) in the promoter (C-589T) and 5′ untranslated region (C-33T) of the IL4 gene have been identified. Polymorphism C-589T was reported to influence total serum IgE levels and bronchial hyperresponsiveness. However, no study has investigated the putative existence of further SNPs in exons, introns, and flanking regions of the IL4 gene. Objective: A complete screening of the IL4 gene and its flanking regions for new polymorphisms was performed. Large-scale association studies in 1120 German schoolchildren were conducted to determine the effect of all polymorphisms present in the IL4 gene on the phenotypic expression of atopic diseases. Methods: Denaturing HPLC and standard sequencing techniques were performed to detect novel polymorphisms in 33 unrelated subjects unselected for atopic diseases. Linkage disequilibrium was assessed for all polymorphisms in the IL4 gene, and association studies were performed. Results: A total of 16 polymorphisms were identified in the IL4 gene, 14 of which were not reported previously. The pattern of linkage disequilibrium observed in IL4 could not be explained by physical distance. A significant association between a cluster of polymorphisms in strong linkage disequilibrium with each other and a physician's diagnosis of asthma and total serum IgE levels was found. Conclusion: These results indicate a possible involvement of SNPs in the IL4 gene in the development of asthma and the regulation of total serum IgE.

Original languageEnglish (US)
Pages (from-to)893-898
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume112
Issue number5
DOIs
StatePublished - Nov 2003

Fingerprint

Interleukin-4
Immunoglobulin E
Asthma
Genes
Linkage Disequilibrium
Single Nucleotide Polymorphism
Serum
5' Untranslated Regions
Introns
Exons
Hypersensitivity
Up-Regulation
High Pressure Liquid Chromatography
Cytokines
Physicians

Keywords

  • Asthma
  • Atopy
  • Childhood
  • IgE
  • IL-13
  • IL-4
  • Polymorphism
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

A complete screening of the IL4 gene : Novel polymorphisms and their association with asthma and IgE in childhood. / Kabesch, Michael; Tzotcheva, Iren; Carr, David; Höfler, Claudia; Weiland, Stephan K.; Fritzsch, Christian; Von Mutius, Erika; Martinez, Fernando.

In: Journal of Allergy and Clinical Immunology, Vol. 112, No. 5, 11.2003, p. 893-898.

Research output: Contribution to journalArticle

Kabesch, Michael ; Tzotcheva, Iren ; Carr, David ; Höfler, Claudia ; Weiland, Stephan K. ; Fritzsch, Christian ; Von Mutius, Erika ; Martinez, Fernando. / A complete screening of the IL4 gene : Novel polymorphisms and their association with asthma and IgE in childhood. In: Journal of Allergy and Clinical Immunology. 2003 ; Vol. 112, No. 5. pp. 893-898.
@article{d2e81285512944b5aa9cb8b180160a39,
title = "A complete screening of the IL4 gene: Novel polymorphisms and their association with asthma and IgE in childhood",
abstract = "Background: IL-4, a cytokine with immunomodulatory functions, is involved in the upregulation of IgE production characteristic of asthma and allergy. Thus far, 2 single nucleotide polymorphisms (SNPs) in the promoter (C-589T) and 5′ untranslated region (C-33T) of the IL4 gene have been identified. Polymorphism C-589T was reported to influence total serum IgE levels and bronchial hyperresponsiveness. However, no study has investigated the putative existence of further SNPs in exons, introns, and flanking regions of the IL4 gene. Objective: A complete screening of the IL4 gene and its flanking regions for new polymorphisms was performed. Large-scale association studies in 1120 German schoolchildren were conducted to determine the effect of all polymorphisms present in the IL4 gene on the phenotypic expression of atopic diseases. Methods: Denaturing HPLC and standard sequencing techniques were performed to detect novel polymorphisms in 33 unrelated subjects unselected for atopic diseases. Linkage disequilibrium was assessed for all polymorphisms in the IL4 gene, and association studies were performed. Results: A total of 16 polymorphisms were identified in the IL4 gene, 14 of which were not reported previously. The pattern of linkage disequilibrium observed in IL4 could not be explained by physical distance. A significant association between a cluster of polymorphisms in strong linkage disequilibrium with each other and a physician's diagnosis of asthma and total serum IgE levels was found. Conclusion: These results indicate a possible involvement of SNPs in the IL4 gene in the development of asthma and the regulation of total serum IgE.",
keywords = "Asthma, Atopy, Childhood, IgE, IL-13, IL-4, Polymorphism, Single nucleotide polymorphism",
author = "Michael Kabesch and Iren Tzotcheva and David Carr and Claudia H{\"o}fler and Weiland, {Stephan K.} and Christian Fritzsch and {Von Mutius}, Erika and Fernando Martinez",
year = "2003",
month = "11",
doi = "10.1016/j.jaci.2003.08.033",
language = "English (US)",
volume = "112",
pages = "893--898",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "5",

}

TY - JOUR

T1 - A complete screening of the IL4 gene

T2 - Novel polymorphisms and their association with asthma and IgE in childhood

AU - Kabesch, Michael

AU - Tzotcheva, Iren

AU - Carr, David

AU - Höfler, Claudia

AU - Weiland, Stephan K.

AU - Fritzsch, Christian

AU - Von Mutius, Erika

AU - Martinez, Fernando

PY - 2003/11

Y1 - 2003/11

N2 - Background: IL-4, a cytokine with immunomodulatory functions, is involved in the upregulation of IgE production characteristic of asthma and allergy. Thus far, 2 single nucleotide polymorphisms (SNPs) in the promoter (C-589T) and 5′ untranslated region (C-33T) of the IL4 gene have been identified. Polymorphism C-589T was reported to influence total serum IgE levels and bronchial hyperresponsiveness. However, no study has investigated the putative existence of further SNPs in exons, introns, and flanking regions of the IL4 gene. Objective: A complete screening of the IL4 gene and its flanking regions for new polymorphisms was performed. Large-scale association studies in 1120 German schoolchildren were conducted to determine the effect of all polymorphisms present in the IL4 gene on the phenotypic expression of atopic diseases. Methods: Denaturing HPLC and standard sequencing techniques were performed to detect novel polymorphisms in 33 unrelated subjects unselected for atopic diseases. Linkage disequilibrium was assessed for all polymorphisms in the IL4 gene, and association studies were performed. Results: A total of 16 polymorphisms were identified in the IL4 gene, 14 of which were not reported previously. The pattern of linkage disequilibrium observed in IL4 could not be explained by physical distance. A significant association between a cluster of polymorphisms in strong linkage disequilibrium with each other and a physician's diagnosis of asthma and total serum IgE levels was found. Conclusion: These results indicate a possible involvement of SNPs in the IL4 gene in the development of asthma and the regulation of total serum IgE.

AB - Background: IL-4, a cytokine with immunomodulatory functions, is involved in the upregulation of IgE production characteristic of asthma and allergy. Thus far, 2 single nucleotide polymorphisms (SNPs) in the promoter (C-589T) and 5′ untranslated region (C-33T) of the IL4 gene have been identified. Polymorphism C-589T was reported to influence total serum IgE levels and bronchial hyperresponsiveness. However, no study has investigated the putative existence of further SNPs in exons, introns, and flanking regions of the IL4 gene. Objective: A complete screening of the IL4 gene and its flanking regions for new polymorphisms was performed. Large-scale association studies in 1120 German schoolchildren were conducted to determine the effect of all polymorphisms present in the IL4 gene on the phenotypic expression of atopic diseases. Methods: Denaturing HPLC and standard sequencing techniques were performed to detect novel polymorphisms in 33 unrelated subjects unselected for atopic diseases. Linkage disequilibrium was assessed for all polymorphisms in the IL4 gene, and association studies were performed. Results: A total of 16 polymorphisms were identified in the IL4 gene, 14 of which were not reported previously. The pattern of linkage disequilibrium observed in IL4 could not be explained by physical distance. A significant association between a cluster of polymorphisms in strong linkage disequilibrium with each other and a physician's diagnosis of asthma and total serum IgE levels was found. Conclusion: These results indicate a possible involvement of SNPs in the IL4 gene in the development of asthma and the regulation of total serum IgE.

KW - Asthma

KW - Atopy

KW - Childhood

KW - IgE

KW - IL-13

KW - IL-4

KW - Polymorphism

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=0242467244&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242467244&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2003.08.033

DO - 10.1016/j.jaci.2003.08.033

M3 - Article

C2 - 14610476

AN - SCOPUS:0242467244

VL - 112

SP - 893

EP - 898

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 5

ER -