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 - 18/08/11
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, Valérie Siroux, PhD , Stefano Guerra, MD, PhD, Walter T. Klimecki, DVM, PhD, Fernando D. Martinez, MDReprint requests: Penelope E. Graves, ScD, Arizona Respiratory Center, University of Arizona, 1501 N Campbell Avenue, PO 245030, Tucson, AZ 85724-5030.Tucson, Ariz
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.
Le texte complet de cet article est disponible en PDF.Key words : Atopy, asthma, eczema, TIM, ITK, polymorphisms
Abbreviations used : CRSP9, HAV, ITK, LD, RR, SNP, SPT, TIM
Plan
| 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. |
Vol 116 - N° 3
P. 650-656 - septembre 2005 Retour au numéro
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