title: Genetic variants in endotoxin signalling pathway, domestic endotoxin exposure and asthma exacerbations.
abstract: BACKGROUND
  We investigated the interaction between genetic variants in endotoxin signalling pathway and domestic endotoxin exposure in relation to asthma presence, and amongst 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 yr). Amongst asthmatics, we extracted data on hospitalization 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 with homozygotes for C allele [OR (95% CI), 0.42 (0.25-0.88), p = 0.01, False Discovery Rate (FDR) p = 0.02]; for LY96 SNP rs17226566, C-allele carriers were at a lower risk of hospital admissions compared with 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).
  
  
  CONCLUSIONS
  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 hospitalization.
authors.affiliation: General Hospital "Dr Josip Bencevic" Slavonski Brod, University of Osijek, Osijek, Croatia.
authors.forename: Blazenka
authors.initials: B
authors.lastname: Kljaic-Bukvic
authors.forename: Mario
authors.initials: M
authors.lastname: Blekic
authors.forename: Neda
authors.initials: N
authors.lastname: Aberle
authors.forename: John A
authors.initials: JA
authors.lastname: Curtin
authors.forename: Jenny
authors.initials: J
authors.lastname: Hankinson
authors.forename: Aida
authors.initials: A
authors.lastname: Semic-Jusufagic
authors.forename: Danielle
authors.initials: D
authors.lastname: Belgrave
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
authors.forename: Adnan
authors.initials: A
authors.lastname: Custovic
mesh_terms: D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004391:Dust / Q000276:immunology; D004731:Endotoxins / Q000276:immunology / Q000378:metabolism*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006760:Hospitalization; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D051218:Lymphocyte Antigen 96 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics
chemical_list: D004391:Dust; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96
keywords: CD14; LY96; TLR4; asthma; children; endotoxin; gene-environment interactions