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

the investigators of the TAHS and MACS

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)331-340
Number of pages10
JournalClinical and Experimental Allergy
Volume49
Issue number3
DOIs
Publication statusPublished - 8 Aug 2019

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Siblings
Single Nucleotide Polymorphism
Meta-Analysis
Logistic Models
Alleles
Gene-Environment Interaction
Skin Tests
Longitudinal Studies
Cohort Studies
Health
Genes

Cite this

@article{92b96d3764ae4514b18ad6da4e517dcc,
title = "Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization",
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.",
keywords = "allergic sensitization, allergy, CD14, gene-environment interaction, genetics, siblings",
author = "{the investigators of the TAHS and MACS} and Lau, {Melisa Y.Z.} and Dharmage, {Shyamali C.} and Burgess, {John A.} and Win, {Aung K.} and Lowe, {Adrian J.} and Lodge, {Caroline J.} and Jennifer Perret and Jennie Hui and Thomas, {Paul S.} and Graham Giles and Thompson, {Bruce R.} and Abramson, {Michael J.} and Walters, {E. Haydn} and Matheson, {Melanie C.} and Allen, {Katrina J.} and Geza Benke and Dowty, {James G.} and Bircan Erbas and Feather, {Iain H.} and Frith, {Peter A.} and Gurrin, {Lyle C.} and Hamilton, {Garun S.} and James, {Alan L.} and Jenkins, {Mark A.} and Johns, {David P.} and James Markos and Southey, {Melissa C.} and Richard Wood-Baker and Barton, {Christopher A.} and Bennett, {Catherine M.} and Cecilie Svanes and Mathias Wjst and {Gomez Real}, Francisco and Russell, {Melissa A.} and Axelrad, {Christine J.} and Hill, {David J.}",
year = "2019",
month = "8",
day = "8",
doi = "10.1111/cea.13290",
language = "English",
volume = "49",
pages = "331--340",
journal = "Clinical & Experimental Allergy",
issn = "0954-7894",
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}

Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization. / the investigators of the TAHS and MACS.

In: Clinical and Experimental Allergy, Vol. 49, No. 3, 08.08.2019, p. 331-340.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization

AU - the investigators of the TAHS and MACS

AU - Lau, Melisa Y.Z.

AU - Dharmage, Shyamali C.

AU - Burgess, John A.

AU - Win, Aung K.

AU - Lowe, Adrian J.

AU - Lodge, Caroline J.

AU - Perret, Jennifer

AU - Hui, Jennie

AU - Thomas, Paul S.

AU - Giles, Graham

AU - Thompson, Bruce R.

AU - Abramson, Michael J.

AU - Walters, E. Haydn

AU - Matheson, Melanie C.

AU - Allen, Katrina J.

AU - Benke, Geza

AU - Dowty, James G.

AU - Erbas, Bircan

AU - Feather, Iain H.

AU - Frith, Peter A.

AU - Gurrin, Lyle C.

AU - Hamilton, Garun S.

AU - James, Alan L.

AU - Jenkins, Mark A.

AU - Johns, David P.

AU - Markos, James

AU - Southey, Melissa C.

AU - Wood-Baker, Richard

AU - Barton, Christopher A.

AU - Bennett, Catherine M.

AU - Svanes, Cecilie

AU - Wjst, Mathias

AU - Gomez Real, Francisco

AU - Russell, Melissa A.

AU - Axelrad, Christine J.

AU - Hill, David J.

PY - 2019/8/8

Y1 - 2019/8/8

N2 - 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.

AB - 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.

KW - allergic sensitization

KW - allergy

KW - CD14

KW - gene-environment interaction

KW - genetics

KW - siblings

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U2 - 10.1111/cea.13290

DO - 10.1111/cea.13290

M3 - Article

VL - 49

SP - 331

EP - 340

JO - Clinical & Experimental Allergy

JF - Clinical & Experimental Allergy

SN - 0954-7894

IS - 3

ER -