{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T01:15:52Z","timestamp":1760577352166,"version":"3.37.3"},"reference-count":31,"publisher":"European Respiratory Society (ERS)","issue":"1","content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2014,8,4]]},"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>Smoking is a notorious risk factor for chronic mucus hypersecretion (CMH). CMH frequently occurs in chronic obstructive pulmonary disease (COPD). The question arises whether the same single-nucleotide polymorphisms (SNPs) are related to CMH in smokers with and without COPD.<\/jats:p><jats:p>We performed two genome-wide association studies of CMH under an additive genetic model in male heavy smokers (\u226520 pack-years) with COPD (n=849, 39.9% CMH) and without COPD (n=1348, 25.4% CMH), followed by replication and meta-analysis in comparable populations, and assessment of the functional relevance of significantly associated SNPs.<\/jats:p><jats:p>Genome-wide association analysis of CMH in COPD and non-COPD subjects yielded no genome-wide significance after replication. In COPD, our top SNP (rs10461985, p=5.43\u00d710<jats:sup>\u22125<\/jats:sup>) was located in the<jats:italic>GDNF-AS1<\/jats:italic>gene that is functionally associated with the<jats:italic>GDNF<\/jats:italic>gene. Expression of<jats:italic>GDNF<\/jats:italic>in bronchial biopsies of COPD patients was significantly associated with CMH (p=0.007). In non-COPD subjects, four SNPs had a p-value &lt;10<jats:sup>\u22125<\/jats:sup>in the meta-analysis, including a SNP (rs4863687) in the<jats:italic>MAML3<\/jats:italic>gene, the T-allele showing modest association with CMH (p=7.57\u00d710<jats:sup>\u22126<\/jats:sup>, OR 1.48) and with significantly increased<jats:italic>MAML3<\/jats:italic>expression in lung tissue (p=2.59\u00d710<jats:sup>\u221212<\/jats:sup>).<\/jats:p><jats:p>Our data suggest the potential for differential genetic backgrounds of CMH in individuals with and without COPD.<\/jats:p>","DOI":"10.1183\/09031936.00093314","type":"journal-article","created":{"date-parts":[[2014,9,19]],"date-time":"2014-09-19T07:42:27Z","timestamp":1411112547000},"page":"60-75","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Dissecting the genetics of chronic mucus hypersecretion in smokers with and without COPD"],"prefix":"10.1183","volume":"45","author":[{"given":"Akkelies E.","family":"Dijkstra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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