Abstract：
Atopic eczema is the most common chronic inflammatory skin disease of early childhood and is often the first manifestation of atopic march. Therefore, one challenge is to identify the risk factors associated with atopic eczema that may also be predictors of atopic disease progression. The aim of this study was to investigate the association of SNPs in hornerin (HRNR) and filaggrin-2 (FLG2) genes with childhood atopic eczema, as well as other atopic phenotypes. Genotyping for HRNR and FLG2 was performed in 188 children younger than 2 years of age, previously screened for the FLG null mutations, and followed at yearly intervals until the age of 6. We demonstrated that risk variants of HRNR rs877776[C] and FLG2 rs12568784[T] were associated with atopic eczema, allergic sensitization, and susceptibility to the complex phenotype-asthma plus eczema. These effects seem to be supplementary to the well-known associations for FLG mutations and may be modulated by gene-gene interactions. Additionally, in children with eczema, these genetic variants may also be considered, along with FLG mutations, as predictive biomarkers for eczema-associated asthma. In conclusion, our results indicate that genetic variants in the epidermal differentiation complex gene could contribute to the pathogenesis of atopic eczema and progression to subsequent allergic disease.
摘要：
特应性湿疹是儿童早期最常见的慢性炎症性皮肤病，通常是特应性三月的首发表现。因此,一个挑战是确定与特应性湿疹相关的危险因素,这些因素也可能是特应性疾病进展的预测因素.这项研究的目的是研究hornerin（HRNR）和filaggrin-2（FLG2）基因中的SNP与儿童特应性湿疹的关系。以及其他特应性表型。在188名2岁以下儿童中进行了HRNR和FLG2的基因分型，先前筛选的FLG无效突变，并每年随访一次，直到6岁。我们证明HRNRrs877776[C]和FLG2rs12568784[T]的风险变异与特应性湿疹有关，过敏性致敏，以及对复杂表型哮喘加湿疹的易感性。这些效应似乎补充了众所周知的FLG突变的关联，并且可能受到基因-基因相互作用的调节。此外,在患有湿疹的儿童中，这些遗传变异也可以考虑，连同FLG突变,作为湿疹相关性哮喘的预测生物标志物。总之,我们的结果表明，表皮分化复合物基因的遗传变异可能有助于特应性湿疹的发病机制和随后的过敏性疾病的进展。
