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Polymorphisms in the interleukin-4 and interleukin-4 receptor ? chain genes confer susceptibility to asthma and atopy in a Caucasian population

Polymorphisms in the interleukin-4 and interleukin-4 receptor ? chain genes confer susceptibility to asthma and atopy in a Caucasian population
Polymorphisms in the interleukin-4 and interleukin-4 receptor ? chain genes confer susceptibility to asthma and atopy in a Caucasian population
Background: IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype.
Objective: To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4R? chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma.
Methods: Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4R? chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England.
Results: Case–control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006).
Conclusion: Our data suggest that polymorphisms in the IL-4 and IL-4R? chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.
asthma, bronchial hyperresponsiveness, cytokines, genes, polymorphisms
0954-7894
1111-1117
Beghé, B.
c20830d1-e2ba-4ddd-af37-7c49dc82311a
Barton, S.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Rorke, S.
ca4b3d19-8862-40e7-8f33-b20da825b08d
Peng, Q.
ca0f24d6-e072-44d9-89ff-6f6d80b0c91e
Sayers, I.
230e01df-0685-438a-9173-df1aead72390
Gaunt, T.
8479c3ec-287c-4f1f-bf5e-821f0cac91f9
Keith, T.P.
70e2a4c6-8750-44ea-805e-d74e3ba1739d
Clough, J.B.
54c3712a-f495-4ba6-b190-73fa0ba2b30f
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Beghé, B.
c20830d1-e2ba-4ddd-af37-7c49dc82311a
Barton, S.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Rorke, S.
ca4b3d19-8862-40e7-8f33-b20da825b08d
Peng, Q.
ca0f24d6-e072-44d9-89ff-6f6d80b0c91e
Sayers, I.
230e01df-0685-438a-9173-df1aead72390
Gaunt, T.
8479c3ec-287c-4f1f-bf5e-821f0cac91f9
Keith, T.P.
70e2a4c6-8750-44ea-805e-d74e3ba1739d
Clough, J.B.
54c3712a-f495-4ba6-b190-73fa0ba2b30f
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Holloway, J.W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a

Beghé, B., Barton, S., Rorke, S., Peng, Q., Sayers, I., Gaunt, T., Keith, T.P., Clough, J.B., Holgate, S.T. and Holloway, J.W. (2003) Polymorphisms in the interleukin-4 and interleukin-4 receptor ? chain genes confer susceptibility to asthma and atopy in a Caucasian population. Clinical & Experimental Allergy, 33 (8), 1111-1117. (doi:10.1046/j.1365-2222.2003.01731.x).

Record type: Article

Abstract

Background: IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype.
Objective: To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4R? chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma.
Methods: Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4R? chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England.
Results: Case–control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006).
Conclusion: Our data suggest that polymorphisms in the IL-4 and IL-4R? chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.

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More information

Published date: August 2003
Keywords: asthma, bronchial hyperresponsiveness, cytokines, genes, polymorphisms

Identifiers

Local EPrints ID: 26932
URI: http://eprints.soton.ac.uk/id/eprint/26932
ISSN: 0954-7894
PURE UUID: b4867536-dfd2-45bb-b7ba-4e540394a760
ORCID for S. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for J.W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 25 Apr 2006
Last modified: 16 Mar 2024 03:22

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Contributors

Author: B. Beghé
Author: S. Barton ORCID iD
Author: S. Rorke
Author: Q. Peng
Author: I. Sayers
Author: T. Gaunt
Author: T.P. Keith
Author: J.B. Clough
Author: S.T. Holgate
Author: J.W. Holloway ORCID iD

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