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- DOI: 10.1111/pai.12258
- PMID: 24902762
- UKPMCID: 24902762
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Genetic variants in endotoxin signalling pathway, domestic endotoxin exposure and asthma exacerbations.
Kljaic-Bukvic, Blazenka; Blekic, Mario; Aberle, Neda; Curtin, John A; Hankinson, Jenny; Semic-Jusufagic, Aida; Belgrave, Danielle; Simpson, Angela; Custovic, Adnan
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2014;.
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Full-text held externally
- DOI: 10.1111/pai.12258
- PMID: 24902762
- UKPMCID: 24902762
Abstract
BACKGROUND: We investigated the interaction between genetic variants in endotoxin signalling pathway and domestic endotoxin exposure in relation to asthma presence, and among children with asthma we explored the association of these genetic variants and endotoxin exposure with hospital admissions due to asthma exacerbations. METHODS: In a case-control study, we analysed data from 824 children (417 asthmatics, 407 controls; age 5-18 years). Amongst asthmatics, we extracted data on hospitalisation for asthma exacerbation from medical records. Endotoxin exposure was measured in dust samples collected from homes. We included 26 single nucleotide polymorphisms (SNPs) in the final analysis (5 CD14, 7LY96 and 14 TLR4). RESULTS: Two variants remained significantly associated with hospital admissions with asthma exacerbations after correction for multiple testing: for CD14 SNP rs5744455, carriers of T allele had decreased risk of repeated hospital admissions compared to homozygotes for C allele (OR [95% CI], 0.42 [0.25-0.88], p=0.01, FDR p=0.02); for LY96 SNP rs17226566, C allele carriers were at a lower risk of hospital admissions compared to T allele homozygotes (0.59 [0.38-0.90], p=0.01, FDR p=0.04). We observed two interactions between SNPs in CD14 and LY96 with environmental endotoxin exposure in relation to hospital admissions due to asthma exacerbation which remained significant after correction for multiple testing (CD14 SNPs rs2915863 and LY96 SNP rs17226566). CONCLUSION: Amongst children with asthma, genetic variants in CD14 and LY96 may increase the risk of hospital admissions with acute exacerbations. Polymorphisms in endotoxin pathway interact with domestic endotoxin exposure in further modification of the risk of hospitalisation. This article is protected by copyright. All rights reserved.