Association of toll-interacting protein gene polymorphisms with atopic dermatitis

In order to detect a possible role of TOLLIP variation in the pathogenesis of AD, we screened the entire coding sequence of the TOLLIP gene by SSCP in 50 AD patients. We identified an amino acid exchange in exon 6 (Ala222Ser) and a synonymous variation in exon 4 (Pro139Pro). Subsequently, these two variations and four additional non-coding polymorphisms (-526 C/G, two polymorphisms in intron 1 and one in the 3'UTR) were genotyped in 317 AD patients and 224 healthy controls.The -526G allele showed borderline association with AD in our cohort (p = 0.012; significance level after correction for multiple testing 0.0102). Haplotype analysis did not yield additional information. Evaluation of mRNA expression by quantitative real-time polymerase chain reaction in six probands with the CC and six with the GG genotype at the -526 C/G locus did not reveal significant differences between genotypes.Variation in the TOLLIP gene may play a role in the pathogenesis of AD. Yet, replication studies in other cohorts and populations are warranted to confirm these association results.Atopic dermatitis (AD) is an inflammatory skin disease characterized by pruritus and chronic or relapsing eczematous lesions that commonly presents during early infancy and affects up to 16% of children [1]. AD has a multifactorial background, with genetic predisposition and environmental factors contributing to disease susceptibility [2]. In industrialized countries AD prevalence has increased during the past decades [3], and it has been postulated in the so-called 'hygiene hypothesis' that the lack of contact to microbial products in early infancy might at least in part be responsible for this increase [4]. There is evidence from prospective studies to support an inverse relationship between AD and exposure to endotoxin, a cell membrane component of gram negative bacteria, early day-care attendance and animal exposure [5].Recognition of microbial products such as endotoxin is mediated by the innate immun