A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema
A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema
复制标题
DOI：
10.1016/j.jaci.2007.07.065
复制
发表时间：
2007-11-01
影响因子：
14.2
通讯作者：
Lee, Young-Ae
中科院分区：
文献类型：
--
作者：
Schulz, Florian;Marenholz, Ingo;Lee, Young-Ae
背景资料：IL-31是一种新的细胞因子，当在转基因小鼠中过度表达时，可诱导类似人类湿疹的严重瘙痒性皮炎，目的：我们旨在评估人类IL-31基因（IL-31）多态性在湿疹遗传易感性中的重要性。标记主要单倍型的单核苷酸多态性在3个独立的欧洲人群，包括690个受影响的家庭进行基因分型。结果：在所有3个研究人群中，我们发现一种常见的IL 31单倍型与非特应性湿疹有显著相关性（合并P = 4.5 × 10（-5））。对健康个体PBMC的分析显示，抗CD 3和抗CD 28刺激强烈诱导IL-31 mRNA表达，与非A单倍型携带者相比，风险单倍型（AA）纯合子个体的IL-31 mRNA表达高3.8倍，表明IL-31基因表达调节的改变是致病因素。我们的研究结果有力地支持了IL-31在异位性湿疹发病机制中的重要作用。临床意义：这项研究提出了非特应性湿疹的第一个遗传危险因素，并表明IL-31诱导的瘙痒在这种疾病的发生中起主要作用，从而为湿疹的预防和治疗提出了新的目标。
Background: IL-31 is a novel cytokine that, when overexpressed in transgenic mice, induces severe itching dermatitis resembling human eczema.Objective: We aimed to evaluate the importance of polymorphisms in the human IL-31 gene (IL31) in the genetic susceptibility to eczema.Methods: We sequenced the entire IL-31 gene, including the promoter region, and determined the haplotype structure. Single nucleotide polymorphisms tagging the main haplotypes were genotyped in 3 independent European populations comprising 690 affected families. An association analysis of IL31 gene variants with atopic and nonatopic eczema was performed.Results: We found significant association of a common IL31 haplotype with the nonatopic type of eczema in all 3 study populations (combined P = 4.5 X 10(-5)). Analysis of PBMCs in healthy individuals revealed a strong induction IL31 mRNA expression on stimulation with anti-CD3 and anti-CD28 that was 3.8-fold higher in individuals homozygous for the risk haplotype (AA) in contrast to non-A haplotype carriers, suggesting that altered regulation of IL-31 gene expression is the disease-causing factor.Conclusion: Our results lend strong support to an important role of IL-31 in the pathogenesis of nonatopic eczema.Clinical implications: This study presents the first genetic risk factor for the nonatopic type of eczema and indicates a primary role of IL-31-induced pruritus in the initiation of this disease, thus proposing a new target for the prevention and therapy of eczema.