{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T21:27:54Z","timestamp":1770326874172,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Genetic modifiers have been identified that increase the risks of lung disease and other complications, such as diabetes in people with cystic fibrosis (CF). Variants in the hemochromatosis gene (<jats:italic>HFE<\/jats:italic>) were reported in a study of adults to be associated with worse lung disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To ascertain the frequency of <jats:italic>HFE<\/jats:italic> variants, particularly C282Y (c.845G\u2009&gt;\u2009A) and H63D (c.187C\u2009&gt;\u2009G) and to determine if they are associated with variations in the onset and early severity of CF lung disease as well as abnormalities in iron status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>We studied with whole genome sequencing and clinical outcome measures in a cohort of 104 children with CF at 5\u20136 years old who were previously found to show an association between aggregated genetic modifiers and an earlier onset and a more severe lung disease phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In our cohort, 23% have H63D and 11% have C282Y. Lung function at age 6 years and <jats:italic>Pseudomonas aeruginosa<\/jats:italic> infections did not differ by <jats:italic>HFE<\/jats:italic> variants, but having C282Y was associated with more pulmonary exacerbations in the first 6 years of life. Three patients have H63D\/C282Y genotype, and all showed phenotypic expression of hemochromatosis with abnormal iron indices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study revealed that the presence of <jats:italic>HFE<\/jats:italic> variant C282Y in people with CF may lead to more severe lung disease manifestations beginning in early childhood. There is a risk of hemochromatosis in CF patients with two <jats:italic>HFE<\/jats:italic> variants, and thus they should be followed for evidence of iron overload.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.71042","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T11:23:50Z","timestamp":1741778630000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Frequency and Potential Implications of <i>HFE<\/i> Genetic Variants in Children With Cystic Fibrosis"],"prefix":"10.1002","volume":"60","author":[{"given":"Leslie","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Wisconsin \u2013 Madison Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-3988","authenticated-orcid":false,"given":"HuiChuan 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