{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T07:23:07Z","timestamp":1778916187432,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"publisher","award":["82DZL002A1"],"award-info":[{"award-number":["82DZL002A1"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>CFTR encodes for a chloride and bicarbonate channel expressed at the apical membrane of polarized epithelial cells. Transepithelial sodium transport mediated by the amiloride-sensitive sodium channel ENaC is thought to contribute to the manifestation of CF disease. Thus, ENaC is a therapeutic target in CF and a valid cystic fibrosis modifier gene. We have characterized SCNN1B as a genetic modifier in the three independent patient cohorts of F508del-CFTR homozygotes. We could identify a regulatory element at SCNN1B to the genomic segment rs168748-rs2303153-rs4968000 by fine-mapping (Pbest = 0.0177), consistently observing the risk allele rs2303153-C and the contrasting benign allele rs2303153-G in all three patient cohorts. Furthermore, our results show that expression levels of SCNN1B are associated with rs2303153 genotype in intestinal epithelia (p = 0.003). Our data confirm that the well-established biological role of SCNN1B can be recognized by an association study on informative endophenotypes in the rare disease cystic fibrosis and calls attention to reproducible results in association studies obtained from small, albeit carefully characterized patient populations.<\/jats:p>","DOI":"10.3390\/genes12101554","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:03:42Z","timestamp":1632960222000},"page":"1554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Consistent Assignment of Risk and Benign Allele at rs2303153 in the CF Modifier Gene SCNN1B in Three Independent F508del-CFTR Homozygous Patient Populations"],"prefix":"10.3390","volume":"12","author":[{"given":"Frauke","family":"Stanke","sequence":"first","affiliation":[{"name":"Clinic for Pediatrics, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), The German Center for Lung Research (D.Z.L.), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Becker","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine, Ernst Moritz Arndt University Greifswald, Germany & xValue GmbH, 47877 Willich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haide Susanne","family":"Ismer","sequence":"additional","affiliation":[{"name":"Clinic for Pediatrics, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"Dunsche","sequence":"additional","affiliation":[{"name":"Clinic for Pediatrics, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Hedtfeld","sequence":"additional","affiliation":[{"name":"Clinic for Pediatrics, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Kontsendorn","sequence":"additional","affiliation":[{"name":"Clinic for Pediatrics, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), The German Center for Lung Research (D.Z.L.), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Maria","family":"Dittrich","sequence":"additional","affiliation":[{"name":"Clinic for Pediatrics, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), The German Center for Lung Research (D.Z.L.), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkhard","family":"T\u00fcmmler","sequence":"additional","affiliation":[{"name":"Clinic for Pediatrics, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), The German Center for Lung Research (D.Z.L.), 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2000946","DOI":"10.1183\/13993003.00946-2020","article-title":"ENaC inhibition in cystic fibrosis: Potential role in the new era of CFTR modulator therapies","volume":"56","author":"Mall","year":"2020","journal-title":"Eur. 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