4.6 Article

Polymorphisms in the interleukin 13 and GATA binding protein 3 genes and the development of eczema during childhood

期刊

BRITISH JOURNAL OF DERMATOLOGY
卷 158, 期 6, 页码 1315-1322

出版社

WILEY
DOI: 10.1111/j.1365-2133.2008.08565.x

关键词

atopy; cytokines; eczema; genetics; single nucleotide polymorphisms

资金

  1. NIAID NIH HHS [R01 AI061471-04, R01 AI061471-03, R01 AI061471-02, R01 AI061471] Funding Source: Medline

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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. Objectives 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 >= 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.

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