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Exposure to siblings in early life modifies the association between CD14 polymorphisms and allergic sensitization in adult life

Melisa Lau, Shyamali Dharmage, Aung Win, John Burgess, Adrian Lowe, Caroline Lodge, Jennifer Perret, Jennie Hui, Stephen Morrison, Paul Thomas, Graham Giles, Haydn Walters, Michael Abramson, Melanie Matheson
European Respiratory Journal 2015 46: OA1471; DOI: 10.1183/13993003.congress-2015.OA1471
Melisa Lau
1Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia
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Shyamali Dharmage
1Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia
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Aung Win
1Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia
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John Burgess
1Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia
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Adrian Lowe
1Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia
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Caroline Lodge
1Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia
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Jennifer Perret
1Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia
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Jennie Hui
2School of Population Health, University of Western Australia, Perth, Western Australia Australia
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Stephen Morrison
3Department of Medicine, University of Queensland, Queensland, Australia
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Paul Thomas
4Inflammation and Infection Research Centre, University of New South Wales, New South Wales, Australia
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Graham Giles
5Cancer Epidemiology Centre, Cancer Council Victoria, Victoria, Australia
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Haydn Walters
6Menzies Research Institute, University of Tasmania, Tasmania, Australia
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Michael Abramson
7School of Public Health & Preventive Medicine, Monash University, Victoria, Australia
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Melanie Matheson
1Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia
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Abstract

Aim: Polymorphisms of CD14 are associated with lower risk of allergic disease in children, but little is known about the effects in adult life and the interaction with microbial exposure. We aimed to examine if the association between CD14 polymorphisms and allergic sensitization (AS) in middle age was modified by sibling exposure in early life.

Methods: A total of 1,214 participants from the Tasmanian Longitudinal Health Study (TAHS) were followed from age 7 to 44 years, with skin prick tests and genotyping for three CD14 polymorphisms (rs2569190, rs5744455 and rs2915863) at the 5th decade follow-up. Data on siblings was collected at baseline. Logistic regression was used to examine the association between CD14 polymorphisms and AS and any interaction with siblings exposure.

Results: Exposure to siblings by 6 months, 2 or 4 years was associated with a significantly reduced risk of AS (p for trend=0.001). Overall, no association between any CD14 polymorphisms and AS was seen. We found evidence of gene-environment interaction (GEI) between rs5744455 and cumulative sibling exposure by 6 months (p=0.03), by 2 (p=0.04) and by 4 years (p=0.04). Amongst carriers of the rs5744455-CC genotype, increasing year of sibling exposure by 6 months (OR=0.55, 95%CI 0.41-0.74), by 2 (0.86, 0.79-0.92) and by 4 years (0.92, 0.89-0.96) was associated with lower risk of AS than those without siblings. No association was seen among CT/TT genotype.

Conclusion: The evidence of protective effect from early life GEI that extends up to middle age in this population-based study suggests that high microbial exposure through contact with siblings may be important for immune development.

  • Genetics
  • Allergy
  • Epidemiology
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Exposure to siblings in early life modifies the association between CD14 polymorphisms and allergic sensitization in adult life
Melisa Lau, Shyamali Dharmage, Aung Win, John Burgess, Adrian Lowe, Caroline Lodge, Jennifer Perret, Jennie Hui, Stephen Morrison, Paul Thomas, Graham Giles, Haydn Walters, Michael Abramson, Melanie Matheson
European Respiratory Journal Sep 2015, 46 (suppl 59) OA1471; DOI: 10.1183/13993003.congress-2015.OA1471

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Exposure to siblings in early life modifies the association between CD14 polymorphisms and allergic sensitization in adult life
Melisa Lau, Shyamali Dharmage, Aung Win, John Burgess, Adrian Lowe, Caroline Lodge, Jennifer Perret, Jennie Hui, Stephen Morrison, Paul Thomas, Graham Giles, Haydn Walters, Michael Abramson, Melanie Matheson
European Respiratory Journal Sep 2015, 46 (suppl 59) OA1471; DOI: 10.1183/13993003.congress-2015.OA1471
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