Association of the toll-like receptor 2 A-16934T promoter polymorphism with severe atopic dermatitis

Background:  Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial pathogenesis and increasing incidence in the Western world. A genetically determined defective function of pattern recognition receptors such as toll-like receptors (TLRs) has been proposed as a candidate mechanism in the pathogenesis of AD.
Aim:  To study the impact of genetic predisposition of five genes encoding for pattern recognition-related molecules for the phenotype of AD.
Methods:  We examined nine different single-nucleotide polymorphism (SNP) frequencies in the genes encoding TLR1, -2, -4, -9 and the adapter molecule TIRAP by PCR with subsequent melting curve analysis in a case/control cohort of 136 adult AD patients and 129 age and gender matched non-atopic, healthy individuals. TLR2-expression and -function in cells from genotyped individuals were analysed.
Results:  For the SNPs examined, similar genotype frequencies were found in both groups. In a subgroup of patients suffering from severe AD (SCORAD >50), a significantly increased representation of the A-allele in position –16934 of the tlr2 gene was present ( P  = 0.004). Constitutive tlr2 mRNA expression in peripheral monocytes was independent of this tlr2 promoter SNP. Stimulation assays indicated that IL-6, but not TNF-α secretion following TLR2 stimulation is reduced in homozygous tlr2 -16934-A allele carriers.
Conclusion:  These data indicate that TLR2 is relevant for the phenotype of severe AD in adults.