Disorders of Iron Metabolism

Andrews, Nancy C.

doi:10.1056/nejm199912233412607

Cited by 1,711 publications

(1,407 citation statements)

References 68 publications

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“…The disorder is characterized by systemic iron overload due to enhanced iron absorption in the small bowel (1). Progressive iron accumulation ultimately leads to organ damage and development of cirrhosis, diabetes mellitus, panhypopituitarism, cardiomyopathy, arthritis, and skin hyperpigmentation (2).…”

Section: Introductionmentioning

confidence: 99%

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Bittencourt

Palácios

Couto

et al. 2002

Braz J Med Biol Res

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The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.

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Section: Introductionmentioning

confidence: 99%

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Bittencourt

Palácios

Couto

et al. 2002

Braz J Med Biol Res

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“…Chelation may significantly reduce total body iron load and decrease the production of hydroxyl and oxygen radicals, thus lessening cellular and target organ damage and eventually enhancing survival in transfusion-dependent MDS patients [1,2,21,22]. Note, however, that the evidence for the use of chelation therapy in patients with MDS is based, not on randomized controlled trials, but on observational studies; including two recent ones which continue to provide evidence of an beneficial association between chelation therapy and iron status [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…The circulating non-transferrin-bound iron produces hydroxyl and oxygen radicals that cause lipid peroxidation and damage to cell membranes, protein, and DNA [2,21], especially in target organs such as heart, liver, and endocrine glands [1,22]. Iron overload is associated with reduced survival: adjusting for transfusion burden, hazard rates increase by 30% for every 500 g/L increase in serum ferritin above the threshold of 1000 μg/L [4].…”

Section: Introductionmentioning

confidence: 99%

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

et al. 2011

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 ABSTRACT Transfusion-dependency and iron overload are common among patients with myelodysplastic syndromes (MDS) treated with red blood cell (RBC) transfusions.Transfusion-dependency is associated with leukemic progression and shorter survival.Guidelines recommend iron chelation therapy to manage iron overload, however little is known about the chelation patterns in daily clinical practice. The objective of this multicenter, retrospective, cross-sectional, observational study was to evaluate iron status and its management in transfusion-dependent MDS patients. A total of 193 patient records from 29 centers were eligible for inclusion. Median patient age was 76 and median age at diagnosis of MDS was 74. Patients had received an average of 13.4+7.6 RBC units in the past four months; 44% had received more than 50 units since their MDS diagnosis. Medium serum ferritin was 1550g/L. Ninety patients (46.6%) received iron chelation therapy with either deferoxamine (41%), deferasirox (36%), and deferoxamine followed by deferasirox (23%). There were no statistically significant differences between chelated and nonchelated patients in terms of IPSS, FAB, and/or WHO status, though chelated patients had received more RBC transfusions (p=0.014).Iron chelation therapy may be underutilized in transfusion-dependent patients.

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“…40 Excess iron catalyses the conversion of hydrogen peroxide to free radicals and leads to oxidative stress in various tissues. 42 Disruptions to HNF TFBSs may perturb CP expression and therefore result in incorrect functioning of the antioxidant mechanism. It is possible that oxidative damage from the presence of excess iron could lead to cell damage and the subsequent formation of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of Ceruloplasmin in a South African cohort presenting with oesophageal cancer

Strickland

Matsha

Erasmus

et al. 2011

Intl Journal of Cancer

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Oesophageal cancer (OC) is a disease characterized by the development of malignant tumors in the epithelial cells lining the oesophagus. It demonstrates marked ethnic variation, with squamous cell carcinoma (SCC) being more prevalent in the Black population and adenocarcinoma (ADC) occurring more often in Caucasians. The etiology of this complex disease has been attributed to a variety of factors, including an excess of iron (resulting in increased tumourigenesis), oesophageal injury and inflammation (due in part to Barrett's oesophagus and smoking among others). The aim of this study was to determine if genetic variations identified in the ceruloplasmin (CP) gene (implicated in iron homeostasis) contribute to OC pathogenesis or susceptibility. The study cohort consisted of 96 unrelated OC patients from the Black Xhosa-speaking South African population and 88 population-matched control individuals. The promoter and coding regions of the CP gene were analyzed for DNA sequence variation using heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis, restriction fragment length polymorphism (RFLP) analysis and semi-automated bidirectional DNA sequencing analysis. Fourteen previously described and four novel variants were identified. Statistically significant associations were revealed for two of the novel variants with OC in this study and could, therefore, potentially contribute to disease susceptibility. In silico analysis of the region of the promoter spanning the identified variants sought to identify putative transcription factor binding sites (TFBSs) that could possibly regulate the expression of CP. To our knowledge, this is the first study to examine CP with respect to OC in the Black South African population.

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Disorders of Iron Metabolism

Cited by 1,711 publications

References 68 publications

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

Molecular analysis of Ceruloplasmin in a South African cohort presenting with oesophageal cancer

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