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Asthma phenotypes based on age-of-onset may be differently influenced by the interaction between variation in toll-like receptor ( TLR )/ CD14  genes and environmental microbes. We examined the associations between single-nucleotide polymorphisms (SNP) in the  TLR / CD14  genes and asthma, and their interaction with proxies of microbial exposure (childhood farm exposure and childhood rural environment). Ten SNPs in four genes ( TLR2, TLR4, TLR6, CD14 ) were genotyped for 1,116 participants from the Tasmanian Longitudinal Health Study (TAHS). Using prospectively collected information, asthma was classified as never, early- (before 13 years) or late-onset (after 13 years). Information on childhood farm exposure/childhood rural environment was collected at baseline. Those with early-onset asthma were more likely to be males, had a family history of allergy and a personal history of childhood atopy. We found significant interaction between  TLR6  SNPs and childhood farm exposure. For those with childhood farm exposure, carriers of the  TLR6 -rs1039559 T-allele (p-interaction = 0.009) and  TLR6 -rs5743810 C-allele (p-interaction = 0.02) were associated with lower risk of early-onset asthma. We suggest the findings to be interpreted as hypothesis-generating as the interaction effect did not withstand correction for multiple testing. In this large, population-based longitudinal study, we found that the risk of early- and late-onset asthma is differently influenced by the interaction between childhood farming exposure and genetic variations.

The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early- and late-onset asthma