Lau, MYZ and Dharmage, SC and Burgess, JA and Win, AK and Lowe, AJ and Lodge, CJ and Perret, J and Hui, J and Thomas, PS and Giles, G and Thompson, BR and Abramson, MJ and Walters, EH and Matheson, MC, investigators of the TAHS and MACS, Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization, Clinical and Experimental Allergy, 49, (3) pp. 331-340. ISSN 0954-7894 (2018) [Refereed Article]
© 2018 John Wiley & Sons Ltd
Background: Markers of microbial exposure are thought to be associated with risk of allergic sensitization; however, the associations are inconsistent and may be related to gene‐environment interactions.
Objective: To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship.
Methods: We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi‐level mixed‐effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random‐effects meta‐analysis.
Results: CD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta‐analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455‐SNP (P = 0.001) but not with the rs2569190‐SNP (P = 0.60). The pooled meta‐analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455‐C‐allele than the T‐allele (OR = 0.83 vs 1.05, respectively).
Conclusion and Clinical Relevance: Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals.
|Item Type:||Refereed Article|
|Keywords:||CD14, allergic sensitization, allergy, gene-environment interaction, genetics, siblings|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Respiratory diseases|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Walters, EH (Professor Haydn Walters)|
|Web of Science® Times Cited:||1|
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