Arshad S H, Karmaus W, Kurukulaaratchy R, Sadeghnejad A, Huebner M, Ewart S
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.
Br J Dermatol. 2008 Jun;158(6):1315-22. doi: 10.1111/j.1365-2133.2008.08565.x. Epub 2008 Apr 10.
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.
We assessed the association of polymorphisms in the IL13 and GATA3 genes with childhood eczema.
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.
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).
A SNP in GATA3 is associated with atopic eczema. This finding highlights the importance of GATA3 as an immune-modulating gene in atopic eczema.
特应性皮炎的特征是Th2主导的免疫反应,细胞因子白细胞介素13和转录因子GATA结合蛋白3发挥关键作用。
我们评估了IL13和GATA3基因多态性与儿童湿疹的关联。
1989年在怀特岛建立了一个出生队列(n = 1456),并在1岁(n = 1167)、2岁(n = 1174)、4岁(n = 1218)和10岁(n = 1373)时进行随访,以确定包括湿疹在内的过敏性疾病的患病率。在4岁和10岁时进行皮肤点刺试验。在10岁评估时采集全血样本(n = 923),冷冻保存并进行基因分型。本次分析对IL13的5个多态性和GATA3的7个多态性进行了基因分型。对1岁、2岁、4岁和10岁时湿疹的发生情况进行了重复测量分析。所有分析均对父母的湿疹、低出生体重(<2500 g)、母乳喂养≥3个月和年龄进行了校正。
IL13与儿童湿疹无关。对于GATA3,单核苷酸多态性(SNP)rs2275806(启动子区域)显示特应性皮炎的比值比增加,与比较组皮肤点刺试验是否阳性无关。与无湿疹的儿童相比,SNP rs444762(内含子3区域)与特应性皮炎相关。仅对rs2275806进行多重检验校正后,增加的相对风险仍具有显著性(P < 0.05)。
GATA3中的一个SNP与特应性皮炎相关。这一发现凸显了GATA3作为特应性皮炎免疫调节基因的重要性。