{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:36:27Z","timestamp":1775144187679,"version":"3.50.1"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1826,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Hemochromatosis gene (<\/jats:bold>\n                                 <jats:bold>\n                                    HFE\n                                 <\/jats:bold>\n                                 <jats:bold>)-associated hereditary hemochromatosis (HH) is a genetic predisposition to iron overload and subsequent signs and symptoms of disease that potentially affects approximately 80,000 persons in Australia and almost 1 million persons in the United States. Most clinical cases are homozygous for the Cys282Tyr (C282Y) mutation in the<\/jats:bold>\n                                 <jats:bold>\n                                    HFE\n                                 <\/jats:bold>\n                                 <jats:bold>gene, with serum ferritin (SF) concentration &gt;1000 \u03bcg\/L as the strongest predictor of cirrhosis. The optimal treatment regimen for those with SF concentrations above the normal range but &lt;1000 \u03bcg\/L is unknown. We assessed<\/jats:bold>\n                                 <jats:bold>\n                                    HFE\n                                 <\/jats:bold>\n                                 <jats:bold>mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An<\/jats:bold>\n                                 <jats:bold>\n                                    HFE\n                                 <\/jats:bold>\n                                 <jats:bold>-stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants'<\/jats:bold>\n                                 <jats:bold>\n                                    HFE\n                                 <\/jats:bold>\n                                 <jats:bold>genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all<\/jats:bold>\n                                 <jats:bold>\n                                    HFE\n                                 <\/jats:bold>\n                                 <jats:bold>wild-types (131 male, 160 female) with baseline and follow-up SF concentrations &lt;1000 \u03bcg\/L were assessed for HH-associated signs and symptoms including abnormal second\/third metacarpophalangeal joints (MCP2\/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH-associated signs and symptoms was similar for C282Y homozygotes and<\/jats:bold>\n                                 <jats:bold>\n                                    HFE\n                                 <\/jats:bold>\n                                 <jats:bold>wild-types for both normal and moderately elevated SF concentrations. The maximum prevalence difference between<\/jats:bold>\n                                 <jats:bold>\n                                    HFE\n                                 <\/jats:bold>\n                                 <jats:bold>genotype groups with moderately elevated SF was 11% (MCP2\/3, 95% confidence interval = \u22126%, 29%;<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.22) and for normal SF was 6% (arthritis medicine use, 95% confidence interval = \u22123%, 16%;<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.11).<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>\n                                 <jats:bold>Previously undiagnosed C282Y homozygotes with SF concentrations that remain below 1000 \u03bcg\/L are at low risk of developing HH-associated signs and symptoms at an age when disease would be expected to have developed. These observations have implications for the management of C282Y homozygotes.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.23786","type":"journal-article","created":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T03:44:34Z","timestamp":1275450274000},"page":"925-933","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":42,"title":["HFE Cys282Tyr Homozygotes With Serum Ferritin Concentrations Below 1000 \u03bcg\/L Are at Low Risk of Hemochromatosis\u2020,\u2021"],"prefix":"10.1097","volume":"52","author":[{"given":"Katrina J.","family":"Allen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine A.","family":"Bertalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Osborne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare C.","family":"Constantine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin B.","family":"Delatycki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy E.","family":"Nisselle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda J.","family":"Nicoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota M.","family":"Gertig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine E.","family":"McLaren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham G.","family":"Giles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"Hopper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory J.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John K.","family":"Olynyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrie W.","family":"Powell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyle C.","family":"Gurrin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-15-20250312","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1056\/NEJMra031573","article-title":"Hereditary hemochromatosis-a new look at an old disease.","volume":"350","author":"Pietrangelo","year":"2004","journal-title":"N Engl J Med"},{"key":"R2-15-20250312","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/S0140-6736(07)61782-6","article-title":"Haemochromatosis.","volume":"370","author":"Adams","year":"2007","journal-title":"Lancet"},{"key":"R3-15-20250312","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0002-9343(99)00120-5","article-title":"A survey of 2,851 patients with hemochromatosis: symptoms and response to treatment.","volume":"106","author":"McDonnell","year":"1999","journal-title":"Am J Med"},{"key":"R4-15-20250312","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/ng0896-399","article-title":"A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.","volume":"13","author":"Feder","year":"1996","journal-title":"Nat Genet"},{"key":"R5-15-20250312","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1089\/10906570050114902","article-title":"Geography of HFE C282Y and H63D mutations.","volume":"4","author":"Merryweather-Clarke","year":"2000","journal-title":"Genet Test"},{"key":"R6-15-20250312","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1001\/jama.285.17.2216","article-title":"Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States.","volume":"285","author":"Steinberg","year":"2001","journal-title":"JAMA"},{"key":"R7-15-20250312","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1056\/NEJMoa073286","article-title":"Iron-overload-related disease in HFE hereditary hemochromatosis.","volume":"358","author":"Allen","year":"2008","journal-title":"N Engl J Med"},{"key":"R8-15-20250312","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1056\/NEJMoa041534","article-title":"Hemochromatosis and iron-overload screening in a racially diverse population.","volume":"352","author":"Adams","year":"2005","journal-title":"N Engl J Med"},{"key":"R9-15-20250312","doi-asserted-by":"crossref","first-page":"209","DOI":"10.7326\/0003-4819-145-3-200608010-00009","article-title":"Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force.","volume":"145","author":"Whitlock","year":"2006","journal-title":"Ann Intern Med"},{"key":"R10-15-20250312","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1001\/archinte.166.3.294","article-title":"Screening for hemochromatosis in asymptomatic subjects with or without a family history.","volume":"166","author":"Powell","year":"2006","journal-title":"Arch Intern Med"},{"key":"R11-15-20250312","doi-asserted-by":"crossref","first-page":"627","DOI":"10.7326\/0003-4819-138-8-200304150-00008","article-title":"Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis.","volume":"138","author":"Morrison","year":"2003","journal-title":"Ann Intern Med"},{"key":"R12-15-20250312","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/S0016-5085(98)70320-8","article-title":"Expression of HLA-linked hemochromatosis in subjects homozygous or heterozygous for the C282Y mutation.","volume":"114","author":"Crawford","year":"1998","journal-title":"Gastroenterology"},{"key":"R13-15-20250312","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1056\/NEJM200011233432104","article-title":"Disease-related conditions in relatives of patients with hemochromatosis.","volume":"343","author":"Bulaj","year":"2000","journal-title":"N Engl J Med"},{"key":"R14-15-20250312","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/gut.2005.070342","article-title":"Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients.","volume":"55","author":"McCune","year":"2006","journal-title":"Gut"},{"key":"R16-15-20250312","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0140-6736(05)63012-7","article-title":"Use of community genetic screening to prevent HFE-associated hereditary haemochromatosis.","volume":"366","author":"Delatycki","year":"2005","journal-title":"Lancet"},{"key":"R17-15-20250312","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/hep.22972","article-title":"HFE C282YH63D compound heterozygotes are at low risk of hemochromatosis-related morbidity.","volume":"50","author":"Gurrin","year":"2009","journal-title":"Hepatology"},{"key":"R18-15-20250312","first-page":"69","article-title":"The Melbourne Collaborative Cohort Study.","volume":"156","author":"Giles","year":"2002","journal-title":"IARC Sci Publ"},{"key":"R21-15-20250312","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1053\/j.gastro.2008.08.056","article-title":"The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis.","volume":"135","author":"Gurrin","year":"2008","journal-title":"Gastroenterology"},{"key":"R23-15-20250312","first-page":"98","article-title":"Arthropathy of genetic hemochromatosis: a major and distinctive manifestation of the disease.","volume":"19","author":"Ines","year":"2001","journal-title":"Clin Exp Rheumatol"},{"key":"R24-15-20250312","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1056\/NEJM199909023411002","article-title":"A population-based study of the clinical expression of the hemochromatosis gene.","volume":"341","author":"Olynyk","year":"1999","journal-title":"N Engl J Med"},{"key":"R25-15-20250312","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1182\/blood-2003-10-3564","article-title":"Hemochromatosis mutations in the general population: iron overload progression rate.","volume":"103","author":"Andersen","year":"2004","journal-title":"Blood"},{"key":"R26-15-20250312","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0140-6736(02)07447-0","article-title":"Penetrance of 845G- A (C282Y) HFE hereditary haemochromatosis mutation in the USA.","volume":"359","author":"Beutler","year":"2002","journal-title":"Lancet"},{"key":"R28-15-20250312","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1155\/2008\/907356","article-title":"Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening.","volume":"22","author":"McLaren","year":"2008","journal-title":"Can J Gastroenterol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.23786","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201009000-00015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T11:01:17Z","timestamp":1741777277000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201009000-00015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.23786","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2010,9]]}}}