Polymorphisms in the interleukin 13 and GATA binding protein 3 genes and the development of eczema during childhood.
BACKGROUND
Atopic eczema is characterized by Th2-dominant immunity with the cytokine interleukin 13 and the transcription factor GATA binding protein 3 playing a critical role.


OBJECTIVE
We assessed the association of polymorphisms in the IL13 and GATA3 genes with childhood eczema.


METHODS
A birth cohort (n = 1456) was established on the Isle of Wight in 1989 and followed at the ages of 1 (n = 1167), 2 (n = 1174), 4 (n = 1218) and 10 years (n = 1373) to determine the prevalence of allergic disease including eczema. At 4 and 10 years, skin prick testing was performed. Whole blood samples (n = 923) were obtained at the 10-year assessment, stored frozen, and genotyped. Five polymorphisms from IL13 and seven from GATA3 were genotyped for this analysis. Repeated measurement analyses were conducted for the occurrence of eczema at ages 1, 2, 4 and 10 years. All analyses were adjusted for maternal and paternal eczema, low birth weight (< 2500 g), breastfeeding >or= 3 months and age.


RESULTS
IL13 was not associated with childhood eczema. For GATA3, the single nucleotide polymorphism (SNP) rs2275806 (promoter region) showed an increased odds ratio for atopic eczema independent of whether the comparison group had a positive skin prick test. The SNP rs444762 (intron 3 region) was associated with atopic eczema in comparison with children without eczema. The increased relative risks remained significant after adjustment for multiple testing only for rs2275806 (P < 0.05).


CONCLUSIONS
A SNP in GATA3 is associated with atopic eczema. This finding highlights the importance of GATA3 as an immune-modulating gene in atopic eczema.
Arshad
S H
SH
The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight and IIR Research Division, University of Southampton, Southampton, UK. sha@soton.ac.uk
Karmaus
W
W
Kurukulaaratchy
R
R
Sadeghnejad
A
A
Huebner
M
M
Ewart
S
S
D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012882:Skin Tests / Q000379:methods; D015854:Up-Regulation
D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D018793:Interleukin-13