BACKGROUND: Toll-like receptors (TLRs) are structurally and functionally related 
and play important roles in the innate and adaptive immune system. By genome 
scanning, evidence of linkage between chromosome Xp22 and asthma and related 
atopic disorders has previously been obtained. Xp22 harbours the TLR7 and TLR8 
genes.
METHODS: The involvement of TLR7 and TLR8 in the aetiology of asthma and related 
disorders was investigated by a family based association analysis of two 
independently ascertained family samples comprising 540 and 424 individuals from 
135 and 100 families, respectively. Ten affected individuals from families 
showing evidence of linkage to Xp22 were screened for sequence variations in 
TLR7 and 8, and nine single nucleotide polymorphisms (SNPs) identified were 
tested for association.
RESULTS: In both samples, significant associations were observed for single SNPs 
and haplotypes of both TLR7 and 8 in all four phenotypes investigated: asthma, 
rhinitis, atopic dermatitis and increased specific IgE. The most significant 
association was seen for rs2407992 (TLR8) in asthma (p = 0.00023, sample A and B 
combined, recessive model). In TLR7, rs179008 showed the strongest association. 
Both rs179008 and rs2407992 are of putative functional significance, potentially 
affecting TLR7 processing and TLR8 splicing, respectively. Haplotypes comprising 
the major alleles of these two SNPs were overtransmitted to the affected 
offspring (eg, p = 0.00012 in asthma, combined sample, additive model).
CONCLUSION: The results provide strong evidence that TLR7 and 8 may confer 
susceptibility to asthma and related atopic disorders and highlight these 
receptors as interesting targets for individualised, causally directed 
treatment.