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Lau, M.Y.Z.* ; Dharmage, S.C.* ; Burgess, J.A.* ; Win, A.K.* ; Lowe, A.J.* ; Lodge, C.J.* ; Perret, J.* ; Hui, J.* ; Thomas, P.S.* ; Giles, G.* ; Thompson, B.R.* ; Abramson, M.J.* ; Walters, E.H.* ; Matheson, M.C.* ; Collaboration (Wjst, M.)

Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization.

Clin. Exp. Allergy 49, 331-340 (2019)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
BackgroundMarkers 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.ObjectiveTo 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.MethodsWe 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 6months, 2 and 4years. 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.ResultsCD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6months, 2 and 4years was each associated with a reduced risk of allergic sensitization at age 45years. A similar effect was observed in MACS. Meta-analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6months 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 6months 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 RelevanceCumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Allergy ; Allergic Sensitization ; Cd14 ; Gene-environment Interaction ; Genetics ; Siblings; Serum Ige Levels; Gene-environment Interactions; Endotoxin Exposure; Soluble Cd14; Promoter Polymorphism; Atopy; Asthma; Association; Diseases; Expression
ISSN (print) / ISBN 0954-7894
e-ISSN 1365-2222
Journal Clinical & Experimental Allergy
Quellenangaben Volume: 49, Issue: 3, Pages: 331-340 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Lung Biology (LHI)