Putative association of a <i>TLR9</i> promoter polymorphism with atopic eczema

TLDR

Toll‑like receptors are central to innate immunity and have been linked to inflammatory disorders, with receptor deficiencies potentially contributing to the high prevalence of atopic diseases. The study aimed to determine whether TLR9 is a susceptibility gene for atopic eczema. Researchers genotyped four tag SNPs in TLR9 across 483 parent‑affected offspring trios and 274 unrelated AE cases versus 252 controls. The C‑1237T promoter variant was significantly associated with atopic eczema in family cohorts—particularly the intrinsic subtype—and showed higher promoter activity in luciferase assays, indicating a potential role in disease susceptibility, though no association was found in the case‑control cohort.

Abstract

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 immunity 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 susceptibility 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.