Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain - IL-2-inducible T-cell kinase gene cluster in chromosome 5q33

Penelope E. Graves, Valérie Siroux, Stefano Guerra, Walter Klimecki, Fernando Martinez

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Background: The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5q33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases. Objective: We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma. Methods: Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n = 508), age 10.8 years (n = 539), and age 16.6 years (n = 424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated. Results: One 15-bp insertion/deletion in exon 4 of TIM1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele = 1.24 [1.07-1.45], P = .005; and 1.43 [1.01-2.01], P = .004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk = 1.28 [1.12-1.47]; P = .0003). SNPs in the 5′ genomic region in ITK, which show moderate linkage disequilibrium with those in TIM3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma. Conclusion: Our findings support a potential role for SNPs in TIM1, TIM3, and ITK, independent of each other, in allergic diseases.

Original languageEnglish (US)
Pages (from-to)650-656
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume116
Issue number3
DOIs
StatePublished - Sep 2005

Fingerprint

Eczema
Mucins
Multigene Family
Chromosomes
T-Lymphocytes
Single Nucleotide Polymorphism
Asthma
Genes
Linkage Disequilibrium
Skin Tests
Allergens
Cell Differentiation
Amino Acid Sequence
Exons
Alleles
Cell Proliferation
Immunoglobulin Domains
emt protein-tyrosine kinase
Proteins

Keywords

  • Asthma
  • Atopy
  • Eczema
  • ITK
  • Polymorphisms
  • TIM

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{e14db8f19b2d43eeb127efbad62abb96,
title = "Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain - IL-2-inducible T-cell kinase gene cluster in chromosome 5q33",
abstract = "Background: The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5q33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases. Objective: We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma. Methods: Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n = 508), age 10.8 years (n = 539), and age 16.6 years (n = 424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated. Results: One 15-bp insertion/deletion in exon 4 of TIM1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele = 1.24 [1.07-1.45], P = .005; and 1.43 [1.01-2.01], P = .004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk = 1.28 [1.12-1.47]; P = .0003). SNPs in the 5′ genomic region in ITK, which show moderate linkage disequilibrium with those in TIM3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma. Conclusion: Our findings support a potential role for SNPs in TIM1, TIM3, and ITK, independent of each other, in allergic diseases.",
keywords = "Asthma, Atopy, Eczema, ITK, Polymorphisms, TIM",
author = "Graves, {Penelope E.} and Val{\'e}rie Siroux and Stefano Guerra and Walter Klimecki and Fernando Martinez",
year = "2005",
month = "9",
doi = "10.1016/j.jaci.2005.05.004",
language = "English (US)",
volume = "116",
pages = "650--656",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
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T1 - Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain - IL-2-inducible T-cell kinase gene cluster in chromosome 5q33

AU - Graves, Penelope E.

AU - Siroux, Valérie

AU - Guerra, Stefano

AU - Klimecki, Walter

AU - Martinez, Fernando

PY - 2005/9

Y1 - 2005/9

N2 - Background: The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5q33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases. Objective: We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma. Methods: Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n = 508), age 10.8 years (n = 539), and age 16.6 years (n = 424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated. Results: One 15-bp insertion/deletion in exon 4 of TIM1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele = 1.24 [1.07-1.45], P = .005; and 1.43 [1.01-2.01], P = .004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk = 1.28 [1.12-1.47]; P = .0003). SNPs in the 5′ genomic region in ITK, which show moderate linkage disequilibrium with those in TIM3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma. Conclusion: Our findings support a potential role for SNPs in TIM1, TIM3, and ITK, independent of each other, in allergic diseases.

AB - Background: The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5q33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases. Objective: We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma. Methods: Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n = 508), age 10.8 years (n = 539), and age 16.6 years (n = 424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated. Results: One 15-bp insertion/deletion in exon 4 of TIM1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele = 1.24 [1.07-1.45], P = .005; and 1.43 [1.01-2.01], P = .004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk = 1.28 [1.12-1.47]; P = .0003). SNPs in the 5′ genomic region in ITK, which show moderate linkage disequilibrium with those in TIM3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma. Conclusion: Our findings support a potential role for SNPs in TIM1, TIM3, and ITK, independent of each other, in allergic diseases.

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