Genetic variants in endotoxin signalling pathway, domestic endotoxin exposure and asthma exacerbations. Issue 6 (October 2014)

• Record Type: Journal Article
• Authors: Kljaic‐Bukvic, Blazenka; Blekic, Mario; Aberle, Neda; Curtin, John A.; Hankinson, Jenny; Semic‐Jusufagic, Aida; Belgrave, Danielle; Simpson, Angela; Custovic, Adnan
• Is Part Of: Pediatric allergy and immunology. Volume 25:Issue 6(2014)
• Page Start: 552
• Page End: 557
• Publication Date: 2014-10
• Subjects: Allergy in children -- Periodicals; Immunologic diseases in children -- Periodicals; 617
• DOI: 10.1111/pai.12258
• Languages: English
• ISSNs: 0905-6157

Abstract

<abstract abstract-type="main" id="pai12258-abs-0001"> <title>Abstract</title> <sec id="pai12258-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="pai12258-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>CD14</italic>, 7<italic>LY96</italic> and 14 <italic>TLR4)</italic>.</p> </sec> <sec id="pai12258-sec-0003" sec-type="section"> <title>Results</title> <p>Two variants remained significantly associated with hospital admissions with asthma exacerbations after correction for multiple testing: for <italic>CD14 </italic>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 <italic>LY96 </italic>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 <italic>CD14</italic> and <italic>LY96</italic> with environmental endotoxin exposure in relation to hospital admissions due to asthma exacerbation which remained significant after correction for multiple testing (<italic>CD14 </italic>SNPs rs2915863 and <italic>LY96 </italic>SNP rs17226566).</p> </sec> <sec id="pai12258-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Amongst children with asthma, genetic variants in <italic>CD14</italic> and <italic>LY96</italic> 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.</p> </sec> </abstract>