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.Allen, K.J.Benke, G.Dowty, J.G.Erbas, B.Feather, I.H.Frith, P.A.et al.2019-08-222019-08-222019Clinical and Experimental Allergy, 2019; 49(3):331-3400954-78941365-2222http://hdl.handle.net/2440/120647BACKGROUND: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.en© 2018 John Wiley & Sons Ltd.Allergy; allergic sensitization; CD14; gene‐environment interaction; genetics; siblingsJournal article003012048510.1111/cea.132900004606760000092-s2.0-85056414581465580Barton, C.A. [0000-0001-9823-7425]