Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization Academic Article uri icon

abstract

  • 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.

authors

  • Lau, MYZ
  • Dharmage, SC
  • Burgess, JA
  • Win, AK
  • Lowe, AJ
  • Lodge, CJ
  • Perret, J
  • Hui, J
  • Thomas, PS
  • Giles, G
  • Thompson, BR
  • Abramson, MJ
  • Walters, EH
  • Matheson, MC
  • Allen, KJ
  • Benke, G
  • Dowty, JG
  • Erbas, Bircan
  • Feather, IH
  • Frith, PA
  • Gurrin, LC
  • Hamilton, GS
  • James, AL
  • Jenkins, MA
  • Johns, DP
  • Markos, J
  • Southey, MC
  • Wood-Baker, R
  • Barton, CA
  • Bennett, CM
  • Svanes, C
  • Wjst, M
  • Gomez Real, F
  • Russell, MA
  • Axelrad, CJ
  • Hill, DJ

publication date

  • 2019

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