Genetic regulators of sputum mucin concentration and their associations with COPD phenotypes

• DOI: 10.1371/journal.pgen.1010445
• Publication Date: 2023-06-24T23:30:35Z
• Authors: Eric Van Buren; Giorgia Radicioni; Sarah Lester; Wanda K. O’Neal; Hong Dang; Silva Kasela; Suresh Garudadri; Jeffrey L. Curtis; MeiLan K. Han; Jerry A. Krishnan; Emily S. Wan; Edwin K. Silverman; Annette Hastie; Victor E. Ortega; Tuuli Lappalainen; Martijn C. Nawijn; Maarten van den B...; Stephanie A. Chri...; Yun Li; Michael H. Cho; Mehmet Kesimer; Samir N. P. Kelada
• Keywords: Genome-wide Association Study; Chronic bronchitis

Hyper-secretion and/or hyper-concentration of mucus is a defining feature multiple obstructive lung diseases, including chronic pulmonary disease (COPD). Mucus itself composed mixture water, ions, salt and proteins, which the gel-forming mucins, MUC5AC MUC5B, are most abundant. Recent studies have linked concentrations these proteins in sputum to COPD phenotypes, bronchitis (CB) acute exacerbations (AE). We sought determine whether common genetic variants influence mucin also associated with specifically CB AE. performed GWAS identify quantitative trait loci for protein concentration (pQTL) Sub-Populations InteRmediate Outcome Measures Study (SPIROMICS, n = 708 total mucin, 215 MUC5AC, MUC5B). Subsequently, we tested associations pQTL AE using regression modeling (n 822-1300). Replication analysis was conducted data from COPDGene 5740) by examining results UK Biobank. identified one genome-wide significant (rs75401036) two MUC5B (rs140324259, rs10001928). The strongest association rs140324259 on chromosome 11, explained 14% variation MUC5B. Despite being lower C allele conferred increased risk (odds ratio (OR) 1.42; 95% confidence interval (CI): 1.10-1.80) as well ascertained over three years follow up (OR 1.41; CI: 1.02-1.94). Associations between or did not replicate COPDGene. However, Biobank, phenotypes that define CB, namely production cough, again conferring risk. conclude variants, top locus may particular CB.