{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T10:34:08Z","timestamp":1773484448663,"version":"3.50.1"},"reference-count":42,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,6,15]]},"abstract":"<jats:p>Severe iron overload usually develops in patients with hereditary hemochromatosis (HHC), but variability in the phenotypic expression of the disease has been reported. This study assessed whether tumor necrosis factor \u03b1 (TNF-\u03b1) plays a role in phenotypic expression of HHC. Sixty-four patients with HHC and 172 healthy volunteers (controls) were studied. Release of TNF-\u03b1 from stimulated peripheral blood monocytes was measured by enzyme-linked immunosorbent assay, and 308 and 238 TNF-\u03b1 polymorphisms were detected with polymerase chain reaction and restriction fragment-length polymorphism analysis. The relation between TNF-\u03b1 polymorphisms and clinical expression of HHC was evaluated. Patients with HHC released less TNF-\u03b1 than controls, but the difference was significant only in homozygotes for the C282Y mutation. The prevalence of the 308 TNF-\u03b1 polymorphism was similar in patients and controls, whereas the prevalence of the 238 polymorphic allele was significantly lower in patients (3% versus 16%;P\u2009=\u2009.002). A lower prevalence of cirrhosis was observed in patients with TNF-\u03b1 polymorphism than in those without it (4 of 15 [27%] versus 28 of 49 [57%]), but the difference was not significant (P\u2009=\u2009.07). In nonhomozygotes for the C282Y mutation, severe liver siderosis was less prevalent in patients with the 308 polymorphism than in those without it (P\u2009=\u2009.05). Alanine aminotransferase (ALT) values were significantly lower in patients with TNF-\u03b1 polymorphism (P\u2009=\u2009.006), even when patients with other hepatotoxic factors were excluded. Multivariate analysis showed that TNF-\u03b1 polymorphism was independently associated with ALT values (P\u2009=\u2009.0008 and P\u2009=\u2009.045, respectively, in homozygotes and nonhomozygotes for the C282Y mutation) and siderosis in nonhomozygotes (P\u2009=\u2009.047). Thus, TNF-\u03b1 appears to play a role in HHC by modulating the severity of liver damage.<\/jats:p>","DOI":"10.1182\/blood.v97.12.3707","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"3707-3712","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":67,"title":["Tumor necrosis factor \u03b1 promoter polymorphisms influence the phenotypic expression of hereditary hemochromatosis"],"prefix":"10.1182","volume":"97","author":[{"given":"Silvia","family":"Fargion","sequence":"first","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Valenti","sequence":"additional","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Dongiovanni","sequence":"additional","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Scaccabarozzi","sequence":"additional","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Ludovica","family":"Fracanzani","sequence":"additional","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Taioli","sequence":"additional","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Mattioli","sequence":"additional","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Sampietro","sequence":"additional","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemino","family":"Fiorelli","sequence":"additional","affiliation":[{"name":"From Dipartimento di Medicina Interna, Universita\u0300di Milano, Ospedale Maggiore IRCCS, Milan, Italy; and Unita\u0300 di Epidemiologia, Ospedale Maggiore IRCCS, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021221053506600_B1","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 hemochromatosis.","volume":"13","author":"Feder","year":"1996","journal-title":"Nat Genet."},{"key":"2020021221053506600_B2","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/S0016-5085(98)70319-1","article-title":"Heterogeneity of hemochromatosis in 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