MUC5AC and inflammatory mediators associated with respiratory outcomes in the British 1946 birth cohort. Issue 6 (25th July 2013)

• Record Type: Journal Article
• Authors: Johnson, Lauren; Shah, Imran; Loh, Andrew X.; Vinall, Lynne E.; Teixeira, Ana S.; Rousseau, Karine; Holloway, John W.; Hardy, Rebecca; Swallow, Dallas M.
• Is Part Of: Respirology. Volume 18:Issue 6(2013)
• Page Start: 1003
• Page End: 1010
• Publication Date: 2013-07-25
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiratory organs -- Periodicals; 612.2
• DOI: 10.1111/resp.12092
• Languages: English
• ISSNs: 1323-7799

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="resp12092-sec-0001" sec-type="section"> <title>Background and objective</title> <p>Dysregulation of respiratory mucins, MUC5AC in particular, has been implicated in respiratory disease and <italic>MUC5AC</italic> expression is up‐regulated in response to environmental challenges and inflammatory mediators. The aim of this study was to examine the effect of genetic variation on susceptibility to common respiratory conditions.</p> </sec> <sec id="resp12092-sec-0002" sec-type="section"> <title>Methods</title> <p>The association of <italic>MUC5AC</italic> and the closely linked genes <italic>MUC2</italic> and <italic>MUC5B</italic> with respiratory outcomes was tested in the MRC National Survey of Health and Development, a longitudinal birth cohort of men and women born in 1946. Also examined were the functional variants of the genes encoding inflammatory mediators, <italic>IL13, IL1B, IL1RN, TNFA</italic> and <italic>ERBB1</italic>, for which there is a likely influence on <italic>MUC5AC</italic> expression and were explored potential gene–gene interactions with these inflammatory mediators.</p> </sec> <sec id="resp12092-sec-0003" sec-type="section"> <title>Results</title> <p>Statistically significant associations between the 3'ter <italic>MUC5AC</italic> simple nucleotide polymorphism (SNP) rs1132440 and various non‐independent respiratory outcomes (bronchitis, wheeze, asthma, hay fever) were reported while the adjacent loci show slight (but largely non‐statistically significant) differences, presumably reflective of linkage disequilibrium (allelic association) across the region. A novel association between bronchitis and a non‐synonymous functional <italic>ERBB1</italic> SNP, rs2227983 (aka epidermal growth factor receptor:R497K, R521K) is also reported and evidence presented of interaction between <italic>MUC5AC</italic> and <italic>ERBB1</italic> and between <italic>MUC5AC</italic> and <italic>IL1RN</italic> with respect to bronchitis. The <italic>ERBB1</italic> result suggests a clear mechanism for a biological interaction in which the allelic variants of epidermal growth factor receptor differentially affect mucin expression.</p> </sec> <sec id="resp12092-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The <italic>MUC5AC</italic> association and the interactions with inflammatory mediators suggest that genetically determined differences in <italic>MUC5AC</italic> expression alter susceptibility to respiratory disease.</p> </sec> </abstract>