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

Lau, Melisa Y. Z., Dharmage, Shyamali C., Burgess, John A., Win, Aung K., Lowe, Adrian J., Lodge, Caroline, Perret, Jennifer, Hui, Jennie, Thomas, Paul S., Morrison, Stephen, Giles, Graham G., Hopper, John, Abramson, Michael J., Walters, E. Haydn and Matheson, Melanie C. (2017) The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early-and late-onset asthma. Scientific Reports, 7 43681. doi:10.1038/srep43681


Author Lau, Melisa Y. Z.
Dharmage, Shyamali C.
Burgess, John A.
Win, Aung K.
Lowe, Adrian J.
Lodge, Caroline
Perret, Jennifer
Hui, Jennie
Thomas, Paul S.
Morrison, Stephen
Giles, Graham G.
Hopper, John
Abramson, Michael J.
Walters, E. Haydn
Matheson, Melanie C.
Title The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early-and late-onset asthma
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2017-03-06
Sub-type Article (original research)
DOI 10.1038/srep43681
Open Access Status DOI
Volume 7
Start page 43681
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract 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.
Formatted abstract
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.
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Document type: Journal Article
Sub-type: Article (original research)
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