Food allergy, dermatologic diseases, and anaphylaxis
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

https://doi.org/10.1016/j.jaci.2005.05.004Get rights and content

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.

Section snippets

Population

The children included in the current analysis were a subset of the 1246 healthy infants recruited in the Tucson Children's Respiratory Study. The enrollment process and study design are described elsewhere.20 Briefly, unselected newborns were enrolled between 1980 and 1984. Parents planning to use a large health maintenance organization in Tucson were contacted shortly after their child's birth. Thereafter, all new siblings were recruited in the study. In the current analysis, only the first

Results

Genotyped children who underwent SPT on at least 1 survey (n = 564) were compared with the children enrolled in the study but who were not included in the current analysis mainly because DNA was not available (n = 524). Participants were more likely to have a father with a higher level of education, and Hispanic parents and were less likely to report eczema than nonparticipants (Table I).

The prevalence of atopy was 39.4%, 54.6%, and 71.2% for year 6 (n = 508), year 11 (n = 539), and year 16 (n = 424)

Discussion

It is well established that genetic factors have a central role in the pathogenesis of allergic diseases.1 Because the TIM gene family and ITK may have a role in allergy-associated immune responses8, 9 and are located in the chromosomic region 5q33, a region repeatedly linked to asthma and allergy,3, 4, 5, 6, 7 we considered these genes as potential candidates for allergic phenotypes. For the first time, 3 SNPs in TIM3 were found related to atopy and eczema, and 2 SNPs in the 5′ genomic region

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    • Cited by (0)

    Supported by HL-66447 and HL-56177 from the National Heart, Lung and Blood Institute. Dr Siroux was supported by the French Foreign Office (Lavoisier Grants) and the Conseil Scientifique National de l'AGIR (Association Grenobloise des Insuffisants Respiratoires).

    Disclosure of potential conflict of interest: None to disclose.

    ∗

    These authors contributed equally to this work.

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    Copyright © 2005 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.