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 5 q 33.
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 5 q 33 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 TIM 1 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 TIM 3 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 TIM 3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma.


CONCLUSIONS
Our findings support a potential role for SNPs in TIM 1, TIM 3, and ITK, independent of each other, in allergic diseases.
Graves
Penelope E
PE
Arizona Respiratory Center, University of Arizona, Tuscon, AZ 85724-5030, USA. pgraves@u.arizona.edu
Siroux
Valérie
V
Guerra
Stefano
S
Klimecki
Walter T
WT
Martinez
Fernando D
FD
D000293:Adolescent; D000595:Amino Acid Sequence; D001249:Asthma / Q000235:genetics; D002648:Child; D002851:Chromatography, High Pressure Liquid; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004485:Eczema / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011991:Receptors, Virus / Q000235:genetics*; D012882:Skin Tests
C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase