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

Scientific Reports - Tập 7 Số 1
Melisa Yi Zhi Lau1, Shyamali C. Dharmage1, John A. Burgess1, Aung Ko Win1, Adrian J. Lowe1, Caroline Lodge1, Jennifer L. Perret1, Jennie Hui2, Paul S. Thomas3, Stephen Morrison4, Graham G. Giles5, John L. Hopper1, Michael J. Abramson6, E. Haydn Walters7, Melanie C. Matheson8
1Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, the University of Melbourne, Victoria, Australia
2School of Population Health, The University of Western Australia, Perth, Australia
3Inflammation and Infection Research Centre, University of New South Wales, Australia
4Department of Medicine, The University of Queensland, Queensland, Australia
5Cancer Epidemiology Centre, Cancer Council Victoria, Victoria, Australia
6School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia
7School of Medicine, University of Tasmania, Tasmania, Australia
8Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

Tóm tắt

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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Tài liệu tham khảo

von Mutius, E. & Vercelli, D. Farm living: effects on childhood asthma and allergy. Nature reviews. Immunology 10, 861–868, doi: 10.1038/nri2871 (2010).

Romagnani, S. Immunologic influences on allergy and the TH1/TH2 balance. The Journal of allergy and clinical immunology 113, 395–400, doi: 10.1016/j.jaci.2003.11.025 (2004).

Okada, H., Kuhn, C., Feillet, H. & Bach, J. F. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clinical and experimental immunology 160, 1–9, doi: 10.1111/j.1365-2249.2010.04139.x (2010).

Loss, G. et al. Prenatal and early-life exposures alter expression of innate immunity genes: the PASTURE cohort study. The Journal of allergy and clinical immunology 130, 523–530 e529, doi: 10.1016/j.jaci.2012.05.049 (2012).

Kanagaratham, C., Camateros, P., Flaczyk, A. & Radzioch, D. Polymorphisms in TOLL-like receptor genes and their roles in allergic asthma and atopy. Recent patents on inflammation & allergy drug discovery 5, 45–56 (2011).

Hemmi, H. & Akira, S. TLR signalling and the function of dendritic cells. Chemical immunology and allergy 86, 120–135, doi: 10.1159/000086657 (2005).

Kim, J. I. et al. Crystal structure of CD14 and its implications for lipopolysaccharide signaling. The Journal of biological chemistry 280, 11347–11351, doi: 10.1074/jbc.M414607200 (2005).

Akira, S., Takeda, K. & Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nature immunology 2, 675–680, doi: 10.1038/90609 (2001).

Kormann, M. S. et al. Toll-like receptor heterodimer variants protect from childhood asthma. The Journal of allergy and clinical immunology 122, 86–92, 92 e81-88, doi: 10.1016/j.jaci.2008.04.039 (2008).

Leung, T. F. et al. The C-159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children. Pediatric allergy and immunology: official publication of the European Society of Pediatric Allergy and Immunology 14, 255–260 (2003).

Klaassen, E. M., Thonissen, B. E., van Eys, G., Dompeling, E. & Jobsis, Q. A systematic review of CD14 and toll-like receptors in relation to asthma in Caucasian children. Allergy, asthma, and clinical immunology: official journal of the Canadian Society of Allergy and Clinical Immunology 9, 10, doi: 10.1186/1710-1492-9-10 (2013).

Lau, M. Y. et al. CD14 polymorphisms, microbial exposure and allergic diseases: a systematic review of gene-environment interactions. Allergy 69, 1440–1453, doi: 10.1111/all.12454 (2014).

Smit, L. A. et al. CD14 and toll-like receptor gene polymorphisms, country living, and asthma in adults. American journal of respiratory and critical care medicine 179, 363–368, doi: 10.1164/rccm.200810-1533OC (2009).

Bieli, C. et al. A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression. The Journal of allergy and clinical immunology 120, 1308–1315, doi: 10.1016/j.jaci.2007.07.034 (2007).

Tan, D. J. et al. Age-of-asthma onset as a determinant of different asthma phenotypes in adults: a systematic review and meta-analysis of the literature. Expert review of respiratory medicine 9, 109–123, doi: 10.1586/17476348.2015.1000311 (2015).

Bonnelykke, K. et al. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. Nature genetics 45, 902–906, doi: 10.1038/ng.2694 (2013).

Hinds, D. A. et al. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. Nature genetics 45, 907–911, doi: 10.1038/ng.2686 (2013).

Nilsson, D. et al. Replication of genomewide associations with allergic sensitization and allergic rhinitis. Allergy 69, 1506–1514, doi: 10.1111/all.12495 (2014).

Eder, W. et al. Toll-like receptor 2 as a major gene for asthma in children of European farmers. The Journal of allergy and clinical immunology 113, 482–488, doi: 10.1016/j.jaci.2003.12.374 (2004).

Matheson, M. C. et al. Cohort Profile: The Tasmanian Longitudinal Health STUDY (TAHS). International journal of epidemiology, doi: 10.1093/ije/dyw028 (2016).

Tan, D. J. et al. Clinical and functional differences between early-onset and late-onset adult asthma: a population-based Tasmanian Longitudinal Health Study. Thorax, doi: 10.1136/thoraxjnl-2015-208183 (2016).

Koponen, P. et al. The association of genetic variants in toll-like receptor 2 subfamily with allergy and asthma after hospitalization for bronchiolitis in infancy. The Pediatric infectious disease journal 33, 463–466, doi: 10.1097/INF.0000000000000253 (2014).

Reijmerink, N. E. et al. Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy. The European respiratory journal 38, 833–840, doi: 10.1183/09031936.00099210 (2011).

Shey, M. S. et al. Single nucleotide polymorphisms in toll-like receptor 6 are associated with altered lipopeptide- and mycobacteria-induced interleukin-6 secretion. Genes and immunity 11, 561–572, doi: 10.1038/gene.2010.14 (2010).

Tizaoui, K., Kaabachi, W., Hamzaoui, K. & Hamzaoui, A. Association of Single Nucleotide Polymorphisms in Toll-like Receptor Genes With Asthma Risk: A Systematic Review and Meta-analysis. Allergy, asthma & immunology research 7, 130–140, doi: 10.4168/aair.2015.7.2.130 (2015).

Kerkhof, M. et al. Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma. Thorax 65, 690–697, doi: 10.1136/thx.2009.119636 (2010).

Potaczek, D. P. et al. An association of TLR2-16934A >T polymorphism and severity/phenotype of atopic dermatitis. Journal of the European Academy of Dermatology and Venereology: JEADV 25, 715–721, doi: 10.1111/j.1468-3083.2010.03812.x (2011).

Smit, L. A. et al. Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology 37, 1602–1608, doi: 10.1111/j.1365-2222.2007.02831.x (2007).

Genuneit, J. Exposure to farming environments in childhood and asthma and wheeze in rural populations: a systematic review with meta-analysis. Pediatric allergy and immunology: official publication of the European Society of Pediatric Allergy and Immunology 23, 509–518, doi: 10.1111/j.1399-3038.2012.01312.x (2012).

Svanes, C. What has the ECRHS told us about the childhood risks of asthma, allergy and lung function? The clinical respiratory journal 2 Suppl 1, 34–44, doi: 10.1111/j.1752-699X.2008.00082.x (2008).

Riedler, J. et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358, 1129–1133, doi: 10.1016/S0140-6736(01)06252-3 (2001).

Braun-Fahrlander, C. et al. Prevalence of hay fever and allergic sensitization in farmer’s children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology 29, 28–34 (1999).

Jenkins, M. A. et al. Validation of questionnaire and bronchial hyperresponsiveness against respiratory physician assessment in the diagnosis of asthma. International journal of epidemiology 25, 609–616 (1996).

Wharton, C. et al. Tracing 8,600 participants 36 years after recruitment at age seven for the Tasmanian Asthma Study. Australian and New Zealand journal of public health 30, 105–110 (2006).

Australian Bureau of Statistics. Australian Standard Classification of Occupations (ASCO). Australian Bureau of Statistics, Canberra Second Edition (1997).

Australian Bureau of Statistics. Statistical geography, volume 1: Australian Standard Geographical Classification (ASGC). Australian Bureau of Statistics, Canberra (2001).

Baldini, M. et al. A Polymorphism* in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. American journal of respiratory cell and molecular biology 20, 976–983, doi: 10.1165/ajrcmb.20.5.3494 (1999).

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