Iron overload in African Americans

Barton, James C.; Edwards, Corwin Q.; Bertoli, Luigi F.; Shroyer, T.W.; Hudson, Sharon L.

doi:10.1016/s0002-9343(99)80248-4

Cited by 106 publications

(62 citation statements)

References 30 publications

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“…Iron overload is relatively common in AA [20][21][22][23][24], but is rarely attributable to homozygosity for HFE C282Y [6,24]. In the present study, all participants lacked C282Y, but some participants classified as cases also had markedly elevated levels of transferrin saturation.…”

Section: Discussionmentioning

confidence: 48%

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Rivers

Barton²,

Gordeuk

et al. 2007

Blood Cells, Molecules, and Diseases

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The ferroportin (FPN1) Q248H polymorphism has been associated with increased serum ferritin (SF) levels in sub-Saharan Africans and in African Americans (AA). AA participants of the HEIRS Study who did not have HFE C282Y or H63D who had elevated initial screening SF (≥300 μg/L in men and ≥200 μg/L in women) (defined as cases) were frequency-matched to AA participants with normal SF (defined as controls) to investigate the association of the Q248H with elevated SF. 10.4% of cases and 6.7% of controls were Q248H heterozygotes (P = 0.257). Q248H homozygosity was observed in 0.5% of the cases and none of the controls. The frequency of Q248H was higher among men with elevated SF than among control men (P = 0.047); corresponding differences were not observed among women. This appeared to be unrelated to selfCorrespondence: Dr. James C. Barton G105, 2022 Brookwood Medical Center Drive Birmingham, AL 35209 Telephone 205-877-2888 FAX 205-877-2039 ironmd@dnamail.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. reports of a previous diagnosis of liver disease. Men with elevated SF were three times more likely than women with elevated SF to have Q248H (P = 0.012). There were no significant differences in Q248H frequencies in men and women control participants. We conclude that the frequency of the FPN1 Q248H polymorphism is greater in AA men with elevated SF than in those with normal SF. NIH Public Access

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Section: Discussionmentioning

confidence: 48%

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Rivers

Barton²,

Gordeuk

et al. 2007

Blood Cells, Molecules, and Diseases

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“…The amount of demonstrable iron in macrophages in HH is minimal until the late stages of the disease (27,(39)(40)(41)(42). By contrast, iron accumulation in the overload diseases Bantu siderosis (in Africa) and Kaschin-Beck (in Asia) is prominent both in mononuclear phagocyte system cells and in hepatic parenchymal cells (43)(44)(45). The organ damage that occurs in HH patients subsequent to the iron accumulation (e.g., liver fibrosis, cirrhosis, hepatocellular carcinomas, and diabetic hyperglycemia caused by pancreatic islet destruction) also occurs in old [32m -/-mice (13,46).…”

Section: Discussionmentioning

confidence: 99%

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Santos¹,

Schilham²,

Rademakers³

et al. 1996

The Journal of Experimental Medicine

181

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Previously, hepatic iron overload resembling that in hereditary hemachromatosis (HH) has been found in beta 2-microglobulin knockout (beta 2m-/-) mice. We have now characterized iron metabolism in beta 2m-/- mice. The mutant mice fail to limit the transfer of iron from mucosal cells into the plasma. Transferrin saturation is abnormally high. Pathologic iron depositions occur predominantly in liver parenchymal cells. Reconstitution with normal hematopoietic cells redistributes the iron from parenchymal to Kupffer cells, but does not correct the mucosal defect. We conclude that (a) iron metabolism is defective in the gut mucosa as well as the liver of beta 2m-/- mice; and (b) a beta 2m-dependent gene product is involved in iron homeostasis. Recently, a novel gene of the major histocompatibility complex class I family, HLA-H, has been found to be mutated in a large proportion of HH patients. Our data provide functional support for the proposed causative role of HLA-H mutations in HH.

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“…Bone marrow aspirate and biopsy specimens were prepared with Wright-Giemsa, Perls' Prussian blue, and hematoxylin and eosin techniques, and analyzed for morphology and iron staining in erythroblasts and macrophages. Specimens of liver obtained by percutaneous biopsy were prepared using hematoxylin and eosin, Mallory's trichrome, and Perls' Prussian blue techniques, and analyzed for hepatocyte and Kupffer cell iron grades, cirrhosis, and other abnormalities [14].…”

Section: Laboratory Methodsmentioning

confidence: 99%

“…Iron overload was defined by (1) serum ferritin concentrations (>300 ng/mL in men or >200 ng/mL in women) unexplained by other known cause, (2) increased stainable hepatocyte or Kupffer cell iron or elevated liver iron concentration determined by atomic absorption spectrometry, or (3) quantitative phlebotomy that yielded !4.0 g iron [14,15]. Each patient was evaluated for complications of iron overload, as appropriate [14,15].…”

Section: Diagnosis Evaluation and Treatment Of Iron Overloadmentioning

confidence: 99%

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Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases

et al. 2006

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We evaluated and treated four white adults (one man, three women) who had iron overload associated with daily ingestion of iron supplements for 7, 15, 35, and 61 years, respectively. We performed HFE mutation analysis to detect C282Y, H63D, and S65C in each patient; in two patients, HFE exons were sequenced. In two patients, direct sequencing was performed to detect coding region mutations of TFR2, HAMP, FPN1, HJV, and ALAS2. Patients 1-4 ingested~153, 547, 1,341, and 4,898 g of inorganic iron as supplements. Patient 1 had hemochromatosis, HFE C282Y homozygosity, and b-thalassemia minor. Patient 2 had spherocytosis and no HFE coding region mutations. Patient 3 had no anemia, a normal HFE genotype, and no coding region mutations in HAMP, FPN1, HJV, or ALAS2; she was heterozygous for the TFR2 coding region mutation V583I (nt 1,747 G?A, exon 15). Patient 4 had no anemia and no coding region mutations in HFE, TFR2, HAMP, FPN1, HJV, or ALAS2. Iron removed by phlebotomy was 32.4, 10.4, 15.2, and 4.0 g, respectively. There was a positive correlation of log 10 serum ferritin and the quantity of iron removed by phlebotomy (P = 0.0371). Estimated absorption of iron from supplements in patients 1-4 was 20.9%, 1.9%, 1.1%, and 0.08%. We conclude that the clinical phenotypes and hemochromatosis genotypes of adults who develop iron overload after ingesting iron supplements over long periods are heterogeneous. Therapeutic phlebotomy is feasible and effective, and would prevent complications of iron overload. Am. J. Hematol. 81:760-767, 2006. V V C 2006 Wiley-Liss, Inc.

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Iron overload in African Americans

Cited by 106 publications

References 30 publications

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases

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