Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron metabolites were measured in liver homogenates and leukocytes of patients with hereditary hemochromatosis (HHC), chronic viral hepatitis, and secondary iron overloading. Iron and ferritin levels in the liver are increased HHC, while in hepatitis only ferritin level is increased. In the leukocytes ferritin concentrations are increased both in HHC and secondary iron loading and less so in viral hepatitis. The leukocytic ferritin level decreased after a course of bleeding sessions and during maintenance therapy for HHC, which can serve as a diagnostically significant sign for evaluating the treatment efficiency.
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PMID:[Indices of iron metabolism in liver homogenates and leukocytes]. 1087 39

The widespread use of the genotype assay that identifies the common C282Y mutation in the HFE gene has allowed an earlier diagnosis to be made in many subjects. A significant number of these patients may have no evidence of phenotypic disease and have a normal serum ferritin level. This phenomenon is more common when the genotype assay is used to screen populations rather than higher-risk groups such as family members of a proband with hereditary hemochromatosis. Moreover, patients with significant iron overload may be wild type for the C282Y mutation and have no other demonstrable mutation of the HFE gene. The HFE genotype assay has recently been found to give a false-positive C282Y homozygous result in half of the subjects in one population screening study due to the presence of a single nucleotide polymorphism (SNP) that interfered with primer binding in the PCR assay. The problem may be overcome by using alternate primers. A number of other groups have confirmed the finding but in a much smaller number of subjects, whereas others found that their assays were not affected by the SNP. The use of the HFE genotype assay as the sole diagnostic criterion for hereditary hemochromatosis is not recommended. The genotype assay should be used as an adjunct to the established methods of demonstrating iron overload and be viewed as a predictor of either the presence of iron overload or the subsequent development of iron overload during an individual's lifetime.
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PMID:Pitfalls in the genetic diagnosis of hereditary hemochromatosis. 1095 53

Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in various clinical situations may tip the immunoregulatory balance unfavorably to allow increased growth rates of cancer cells and infectious organisms, and complicate the clinical management of preexisting acute and chronic diseases.
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PMID:Effects of iron overload on the immune system. 1104 59

We describe a case of homozygosity due to the substitution of aspartic acid with histidine at position 63 of the protein encoded by the gene (known as HFE) associated with hereditary hemochromatosis. Liver biopsy did not disclose stainable iron accumulation; serum ferritin was elevated (639 ng/mL), while the transferrin saturation index was within the normal range (38.1%). As the patient was affected by chronic hepatitis C virus, the high serum ferritin could be attributed to this disease, a frequent occurrence. We also describe a case of heterozygosity for both the substitution of tyrosine with cysteine at position 282 and the substitution of histidine to aspartic acid at position 63 (so-called "compound heterozygosity"). The patient had the typical biochemical abnormalities of iron overload: transferrin saturation index of 53.1% and elevated serum ferritin (658 ng/mL). The removal of > 5 g of iron by phlebotomies did not precipitate iron deficiency. Although the patient refused to undergo liver biopsy, clinical evidence alone enabled a diagnosis of hemochromatosis. These two cases concord with the present scientific orientation, i.e.: 1) homozygosity for the major mutation is associated with the phenotypical (clinical) picture of hemochromatosis, but compound heterozygosity also determines significant iron metabolism abnormalities; 2) homozygosity for the minor mutation does not appear to determine important phenotypical abnormalities.
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PMID:[Significance of "minor" genetic mutations in hereditary hemochromatosis: 2 case reports]. 1105 64

Expression of wild type HFE reduces the ferritin levels of cells in culture. In this report we demonstrate that the predominant hereditary hemochromatosis mutation, C282Y(2) HFE, does not reduce ferritin expression. However, the second mutation, H63D HFE, reduces ferritin expression to a level indistinguishable from cells expressing wild type HFE. Further, two HFE cytoplasmic domain mutations engineered to disrupt potential signal transduction, S335M and Y342C, were functionally indistinguishable from wild type HFE in this assay, as was soluble HFE. These results implicate a role for the interaction of HFE with the transferrin receptor in lowering cellular ferritin levels.
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PMID:Interactions of the ectodomain of HFE with the transferrin receptor are critical for iron homeostasis in cells. 1107 91

Screening for hereditary hemochromatosis (HHC) by means of transferrin saturation (TS) levels has been advocated and will identify many patients who are asymptomatic. The purposes of this study were (1) to determine HFE genotypes among asymptomatic HHC patients and correlate this profile with the degree of iron overload and (2) to evaluate the relationship between mobilized iron (mob Fe), age, serum ferritin (SF), and quantitative hepatic iron (QHI) in this population. One hundred twenty-three asymptomatic HHC patients were evaluated; all had quantitative phlebotomy to determine mob Fe and genotyping for C282Y and H63D mutations. Liver biopsies with QHI determinations were performed on 72 of the 123 patients. Of the entire group, 60% were homozygous for C282Y, and 13% were compound heterozygotes (C282Y/H63D). Among asymptomatic patients, the prevalence of homozygous C282Y is lower compared with previous studies that include clinically affected patients. Of those patients with more than 4 g mob Fe, 77% were homozygous C282Y. Asymptomatic patients with lower iron burdens frequently had genotypes other than homozygous C282Y. There was no correlation between age and mob Fe in these patients; however, there was a correlation between mob Fe and both SF (r = 0.68) and QHI (r = 0.75). In conclusion, asymptomatic patients with moderate iron overload had a different genotypic profile than was seen in advanced iron overload. The significance of identifying patients with modest degrees of iron loading, who may not be homozygous for C282Y, must be addressed if routine TS screening is to be implemented. (Blood. 2000;96:3707-3711)
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PMID:Asymptomatic hemochromatosis subjects: genotypic and phenotypic profiles. 1109 50

Despite the clinical use of deferoxamine for more than a quarter of a century, pharmacokinetic studies are few and have not been performed explicitly in patients with sickle cell disorders. Early studies with Intravenous administration to healthy volunteers and patients with transfusional overload showed that although peak concentrations of deferoxamine were similar in both groups, concentrations of ferrioxamine were higher in the latter. In iron-overloaded patients with hereditary hemochromatosis, an intramuscular 10 mg/kg bolus of deferoxamine gave maximal plasma ferrioxamine concentrations exceeding those of deferoxamine, whereas in normal controls the reverse was the case. In more recent studies with homozygous beta-thalassemia, using continuous Intravenous deferoxamine infusion at 50 mg/kg/d, and initial elimination half-life of 0.28/h and steady-state concentration of 7 micromol/L were observed. In these studies, steady-state plasma levels of the predominant deferoxamine metabolite B were usually lower than those of unmetabolized deferoxamine. In a further intravenous infusion study, the proportion of plasma metabolites was higher in those thalassaemia patients with low serum ferritin levels relative to their current mean daily deferoxamine dose, suggesting that high metabolite levels may predict excessive desferrioxamine dosing. This hypothesis is supported by subcutaneous studies in which low doses of slow-release depot deferoxamine resulted in significantly lower proportions of plasma metabolites than with conventional 8-hour infusions at 40 mg/kg. Because serum ferritin is particularly unreliable as a marker of iron overload in sickle cell disorders, measurement of metabolites or the relative proportions of deferoxamine and ferrloxamine may help identify patients at risk of excessive dosing. Because iron overload is likely to become an increasing issue in patients with sickle cell disorders, studies of the pharmacokinetics and metabolism of deferoxamine in this patient group are needed.
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PMID:Deferoxamine pharmacokinetics. 1120 63

Some reports have associated iron with cancer risk, particularly of the colorectum. This review will focus on the human studies that have investigated this association. Comparative studies were sought in which people with and without colorectal neoplastic lesions, either cancers or adenomatous polyps, were assessed for iron exposure. Iron exposure variables included dietary iron intake, iron vitamin supplementation, body iron stores as measured by ferritin or transferrin saturation, and gene status for hereditary hemochromatosis. Medline was searched for published reports using the key words iron, cancer, colon, rectum, ferritin, transferrin, and hemochromatosis. In addition, the Cochrane Library was searched for relevant studies and several authors were contacted to investigate their awareness of unpublished studies. Studies were categorized by study design and ranked for quality of innovation in design, sample size, and thoroughness of iron status ascertainment. Thirty-three studies were reviewed in 26 publications. Of the larger studies, approximately three-quarters supported the association of iron, in all three strata of exposure, with colorectal neoplasia risk. Because iron is broadly supplemented in the American diet, the benefits of iron supplementation need to be measured against the long-term risks of increased iron exposure, one of which may be increased risk of colorectal cancer.
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PMID:Iron and colorectal cancer risk: human studies. 1166 42

We evaluated the iron status and searched for mutations C282Y and H63D in the hereditary hemochromatosis gene (HFE) in 34 pyruvate kinase (PK)-deficient patients from 29 unrelated families. Nine had received multiple transfusions. Thirteen of the 25 nontransfused patients displayed increased serum ferritin concentration, in the absence of conditions known to raise this parameter. HFE genotype was abnormal in 9 of 34 patients. The allele frequency was 1.8% for mutation 845G--> (C282Y) and 16.1% for mutation 187C-->G (H63D). Nontransfused subjects with abnormal genotype had serum ferritin and transferrin saturation values significantly higher than those with wild-type genotype. Of the 12 adult nontransfused patients with increased iron status parameters, 1 was C282Y homozygous, 1 compound heterozygous for C282Y and H63D, 3 H63D heterozygous, and 7 had a normal HFE genotype. Serum ferritin and transferrin saturation were not related to hemoglobin, reticulocytes, and bilirubin concentration. At multivariate analysis serum ferritin was independently associated with age and gender, but not with splenectomy and HFE genotypes. The retrospective evaluation of the iron status profile of 10 patients (3 with abnormal and 7 with wild-type HFE genotype) with at least 10 years follow-up showed that overt iron accumulation requiring iron chelation had occurred only in the 3 patients (2 of whom were splenectomized) with the mutated HFE gene.
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PMID:Iron status and HFE genotype in erythrocyte pyruvate kinase deficiency: study of Italian cases. 1148 80

Homozygosity for the C282Y mutation of the HFE gene is a highly significant risk factor for the development of hereditary hemochromatosis (HH) and the majority of patients with HH have this genotype. An Irish/Belgian female with an elevated serum ferritin level and a family history of hemochromatosis was tested for the presence of the C282Y and H63D mutations. Results of digested PCR products have shown the patient to be homozygous for C282Y mutation and heterozygous for H63D mutation. Sequencing confirmed these findings. Genotyping of the patient's offspring and husband has also indicated the inheritance of both C282Y and H63D in 'cis'. Implications of this finding are: 1) the compound heterozygous state is by far the most common, but not the universal, phase for individuals found to be heterozygous for the two mutations, C282Y and H63D; 2) the C282Y and H63D mutations in the 'cis' phase may account for some cases of questionable parentage.
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PMID:Hemochromatosis mutations C282Y and H63D in 'cis' phase. 1153 73


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