Abstract
Atopic dermatitis (AD) is a chronic, pruritic skin condition with a complex etiology. A few investigators have found associations between cytokine-related genes that modulate the immune response and AD. A defective skin barrier, which could also be influenced by specific genes, has also been implicated in the pathogenesis of AD. However, data is lacking for children of African-American descent. In addition, the relationship between immune genes and skin barrier function has not been evaluated. Also, previous investigations that have used trans-epidermal water loss (TEWL) as a measure of skin barrier function in AD have yielded inconsistent results. This research had two main objectives: to investigate the association between cytokine-related gene polymorphisms and AD and examine whether these polymorphisms influence TEWL; and to determine if children with AD have inherently altered skin barrier function by comparing TEWL in children with and without AD. In a case-control study, we genotyped five single nucleotide polymorphisms (SNPs) in three cytokine-related genes, Interleukin ( IL)4 C-589T, IL4Receptor Alpha (IL4RA) I75V, IL4RA E400A, IL13 R130Q and IL13 C-1112T in a large group of children of Caucasian and African-American descent. We also assessed TEWL in a subset of these children. We tested the association between individual polymorphisms and AD, examined gene-gene interactions, and also investigated the association between different genotypes and TEWL. We further compared TEWL between children with and without AD. Our results showed that the IL4RA E400 allele was associated with AD in African-American children. In Caucasian children with AD, the IL4RA 400A allele was associated with asthma/allergic rhinitis, and the IL13-1112T allele influenced AD severity. TEWL, which positively correlated with AD disease severity, was elevated in children with AD when compared with control groups at most of the anatomical sites tested. However, TEWL was not significantly associated with any of the genes examined in this study. Polymorphisms in cytokine-related genes could influence the phenotype in AD. Skin barrier function, as assessed by TEWL, is compromised in children with AD.