title: The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early- and late-onset asthma.
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.
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.
authors.forename: Melisa Y Z
authors.initials: MY
authors.lastname: Lau
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.|Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
authors.forename: Shyamali C
authors.initials: SC
authors.lastname: Dharmage
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Burgess
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.
authors.forename: Aung K
authors.initials: AK
authors.lastname: Win
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.|Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Lowe
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.|Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lodge
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Perret
authors.affiliation: School of Population Health, the University of Western Australia, Perth, Australia.
authors.forename: Jennie
authors.initials: J
authors.lastname: Hui
authors.affiliation: Inflammation and Infection Research Centre, University of New South Wales, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thomas
authors.affiliation: Department of Medicine, the University of Queensland, Queensland, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Morrison
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Victoria, Australia.|School of Public Health &Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Hopper
authors.affiliation: School of Public Health &Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Abramson
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.|School of Medicine, University of Tasmania, Tasmania, Australia.
authors.forename: E Haydn
authors.initials: EH
authors.lastname: Walters
authors.affiliation: Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia.|Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Matheson
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001249:Asthma / Q000453:epidemiology* / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D004781:Environmental Exposure; D000072480:Farms; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012424:Rural Population; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051216:Toll-Like Receptor 6 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors