Original article Putative association of a TLR9 promoter polymorphism with atopic eczema The aetiology of atopic diseases such as asthma, allergic rhino-conjunctivitis and atopic eczema (AE) is complex and multifactorial, involving both genetic and environ- mental components (1). As possible cause for the increase in prevalence of allergic diseases seen in Western coun- tries over the past decades, it has been suggested that an altered stimulation of innate immune responses during childhood contributes to a deregulated immune response because of a reduction of regulatory T lymphocyte activities and missing immune deviation from allergen- specific immune responses of the Th2 type to protective immune responses of the Th1 type (2). This, in turn, might lead to the manifestation of atopic diseases in genetically susceptible hosts (3, 4). As a complex sequence of events, recognition of microbial components involves innate and acquired immunity mechanisms (5). To discriminate between diverse pathogen associated molecular patterns (PAMPs), our innate immune system uses a variety of pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) or intracellular nucleo- tide-binding oligomerization domain (NOD) proteins (6). Background: Toll-like receptors (TLR) play a pivotal role in the induction of first-line defense mechanisms of the innate immune system and trigger adaptive immune responses to microbial pathogens. Genetic variations in innate immu- nity genes have been reported to be associated with a range of inflammatory disorders. Deficiencies on the level of immunity receptors such as pathogen- recognition receptors are suspected to affect the maturation of our immune system and to avail thereby the high prevalence of atopic diseases and suscep- tibility of atopic patients to microbial infections. Aims of the study: We evaluated TLR9 as susceptibility gene for atopic eczema (AE). Methods: Analyses of four tag single-nucleotide polymorphisms in two panels of families containing a total of 483 parent-affected offspring trios as well as a cohort of 274 unrelated adult AE cases and 252 hypernormal population-based controls have been performed. Results: In both family cohorts, polymorphism C-1237T, which is located within the promoter region of the TLR9 gene, was significantly associated with AE, in particular the intrinsic subtype of AE. No associations were seen in the case– control cohort. Luciferase reporter gene assays revealed significantly higher promoter activity of the TT allelic variant at this single nucleotide polymorphism site. Conclusion: These observations suggest that the TLR9 promoter polymorphism C-1237T might affect AE susceptibility in particular in patients with the intrinsic variant of AE. N. Novak 1,4 , C.-F. Yu 1 , C. Bussmann 1 , L. Maintz 1 , W.-M. Peng 1 , J. Hart 1 , T. Hagemann 1 , A. Diaz-Lacava 2 , H.-J. Baurecht 3 , N. Klopp 4 , S. Wagenpfeil 3 , H. Behrendt 5 , T. Bieber 1 , J. Ring 5 , T. Illig 4 , S. Weidinger 5 1 Department of Dermatology, University of Bonn, Bonn; 2 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn; 3 Institute for Medical Statistics and Epidemiology, Technical University of Munich, Munich; 4 Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg; 5 Department of Dermatology and Allergy Biederstein, Technical University Munich, Germany and Division Environmental Dermatology and Allergy, GSF- National Research Center for Environment and Health and ZAUM Center for Allergy and Environment, Technical University of Munich, Munich, Germany Key words: atopic eczema; immunglobulin E; innate immunity; polymorphisms; toll-like receptor. Natalija Novak Department of Dermatology University of Bonn Sigmund-Freud-Str. 25 53105 Bonn Germany Accepted for publication 6 February 2007 Abbreviations: AE, atopic eczema; CTR, controls; DC, dendritic cells; IgE, immunglobulin E; LD, linkage disequilibrium; MAF, minor allele frequency; NOD, nucleotide-binding oligomerization domain; PAMP, pathogen associated molecular patterns; PBMC, peripheral blood mononuclear cells; pDC, plasmacytoid dendritic cells; PRR, pattern recognition receptors; SNP, single nucleotide polymorphism; TDT, transmission disequilibrium test; TLR, toll- like receptor. Allergy 2007: 62: 766–772 Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2007.01358.x 766