Hereditary hemochromatosis: update for 2003

Harrison, Stephen A.; Bacon, Bruce R.

doi:10.1016/s0168-8278(02)00428-2

Cited by 58 publications

(23 citation statements)

References 99 publications

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“…Much of this NTBI will be cleared by the liver after it is reduced to Fe 2+ [54,58], and strong evidence exists for the presence of ferrireductase activity at the cell surface of hepatocytes [39] and other cell types [24,26]. Notably, DMT1 is upregulated at the plasma membrane of hepatocytes in iron overload [53] and is also expressed in the heart [19,23,27], a major site of iron toxicity in overload [20]. Thus, H + -uncoupled Fe 2+ transport mediated by DMT1 expressed at the plasma membrane can account for the hepatic accumulation of NTBI and directly contribute to the etiology of hepatic and cardiac toxicity in iron overload disorders.…”

Section: Transport Of Znmentioning

confidence: 99%

Divalent metal-ion transporter DMT1 mediates both H+ -coupled Fe2+ transport and uncoupled fluxes

Mackenzie

Ujwal

Chang

et al. 2005

Pflugers Arch - Eur J Physiol

134

185

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The H + -coupled divalent metal-ion transporter DMT1 serves as both the primary entry point for iron into the body (intestinal brush-border uptake) and the route by which transferrin-associated iron is mobilized from endosomes to cytosol in erythroid precursors and other cells. Elucidating the molecular mechanisms of DMT1 will therefore increase our understanding of iron metabolism and the etiology of iron overload disorders. We expressed wild type and mutant DMT1 in Xenopus oocytes and monitored metal-ion uptake, currents and intracellular pH.

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Section: Transport Of Znmentioning

confidence: 99%

Divalent metal-ion transporter DMT1 mediates both H+ -coupled Fe2+ transport and uncoupled fluxes

Mackenzie

Ujwal

Chang

et al. 2005

Pflugers Arch - Eur J Physiol

134

185

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“…Hemochromatosis is a MHC class I -like molecule that regulates duodenal iron absorption when stabilized by h2-miocroglobulin and bound to cell surface -associated transferrin receptor (14). Hemochromatosis Tyr282 homozygotes fail to properly assemble the HFE-h2m-TFR complex and are at increased risk of iron accumulation and its sequelae (15).…”

Section: Introductionmentioning

confidence: 99%

Investigation of Genetic Variants of Genes of the Hemochromatosis Pathway and Their Role in Breast Cancer

Abraham

Justenhoven²,

Pesch³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Iron overload has been noticed as a feature of human breast cancer. Cellular iron uptake is regulated by the hemochromatosis and transferrin receptor system, mutations of which cause the iron storage disease hereditary hemochromatosis. To understand the role of hemochromatosis and transferrin receptor system mutations in breast cancer, we analyzed 19 sequence variations at HFE, TFR1, TFR2, and FPN1 and compared genotype frequencies between cases and controls in a German population. There were 688 breast cancer patients and 724 population-based and age-matched controls. For genotyping, we applied the Hemochromatosis Strip Assay and TaqMan allelic discrimination analyses. In addition to genotype frequencies, we established frequencies of compound genotypes. The frequencies of HFE at His63Asp, Ser65Cys, and Cys282Tyr, and of TFR1 at Ser142Gly minor alleles in this German population were 15.9%, 1.8%, 5.6%, and 46.0%, respectively. No rare variants at 15 more loci at HFE, TFR2, and FPN1 were observed in breast cancer patients. There were no significant differences of allele and genotype frequencies between cases and controls. Triple and quadruple compound genotypes at HFE _His63_Cys282-TFR1 _Ser142Gly and HFE _His63_-Ser65_Cys282-TFR1_Ser142Gly showed a nonsignificant increase in cases. Although limited by low numbers, an increased prevalence of the HFE Tyr282 minor allele was observed in breast cancer cases with a high number of affected lymph nodes (P = 0.032). Our data suggest that variants of the hemochromatosis-transferrin receptor system have no direct effect on the incidence of breast cancer in Germany. Possible effects on tumor progression and prognosis remain elusive.

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“…Bacon and colleagues, found in their study that there had been no fibrosis in liver biposies of the patients whose liver enzymes were normal and who was under 40 years of age. Liver biopsy is not recommended for C282Y homozygous patients who are under 40 years of age and whose liver enzymes are normal and serum ferritin is below 1000 ng / mL (21,45). In a study of 197 C282Y homozygous patients in France, Guyader and colleagues found that there were severe fibrosis in liver biopsy in patients with normal AST levels without hepatomegaly by pyhsical examination and whose ferritin levels under 1000 ng/mL (44).…”

Section: Discussionmentioning

confidence: 99%