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

The frequency of the HLA linked iron-loading gene was assessed in 1783 Afrikaner men over the age of 40 years living in the South Western Cape. Measurements, made on three occasions over a 4.5 year period, included the serum ferritin concentration, a screening test for reduced unsaturated iron-binding capacity and the percentage transferrin saturation. The serum gamma-glutamyl transferase concentration was used as a marker of alcohol abuse. The diagnosis of homozygosity was based on a serum ferritin concentration that was persistently greater than 400 micrograms l-1 and a percentage transferrin saturation greater than 55%. Using these criteria, 17 subjects were diagnosed as homozygous, corresponding to a disease frequency of 0.0095, a gene frequency of 0.0976 and a heterozygote frequency of 0.176 (95% confidence limits: 0.135-0.213). None of the subjects had overt clinical haemochromatosis. Typing for the HLA-A, -B, -C and -DR loci showed that the HLA-A3 allele (frequency 0.6471 and relative risk 4.4) was the only independent marker for the iron-loading gene in this asymptomatic population. Using the present approach it was not possible to distinguish between heterozygotes, alcohol abusers and normal subjects with serum ferritin concentrations at the upper end of the normal range.
 ...
PMID:Phenotypic expression of the HLA linked iron-loading gene in males over the age of 40 years: a population study using serial serum ferritin estimations. 197 75

Hemochromatosis is an autosomal recessive genetic disorder that occurs with high prevalence in populations of European origin. The gene that is abnormal in hemochromatosis is found on the short arm of chromosome 6 in close proximity (approximately 1 centimorgan) to HLA-A, but the product coded for by that gene is unknown. The pathogenetic mechanism in hemochromatosis is that of continued, excessive absorption of dietary iron with loss of normal control mechanisms, leading to a gradual but vast expansion of storage iron as ferritin and especially as hemosiderin. Through mechanisms that probably include peroxidation of lipid membranes, the excess iron injures hepatocytes, islet B cells, gonadotropes in the anterior pituitary, myocardium, synovial cells, and chondrocytes, and probably other cells and tissues as well. Most patients with hemochromatosis remain undiagnosed throughout life. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis when begun early and will significantly improve survival in virtually all patients. It is important, therefore, that the diagnosis of hemochromatosis be considered much more frequently in clinical medicine in order that this effective therapy be utilized.
 ...
PMID:Overview of hemochromatosis. 221 95

The gene for idiopathic haemochromatosis is located on the short arm of chromosome 6 within 1 cM of the HLA-A locus. In this region there are many HLA class I genes, and there may also be a gene for the 'H' subunit of ferritin. Both HLA class I and H ferritin genes are therefore candidates for the abnormal gene in idiopathic haemochromatosis. In 15 unrelated patients the frequency of HLA-A3 was 80% compared with 24% for 600 unrelated individuals from South Wales. The most common haplotype involved is probably HLA-A3, B7. DNA was prepared from leucocytes from 12 of these patients and from 85 normal subjects. After digestion with Taq1, electrophoresis, and Southern blotting, class I sequences were detected by hybridisation to an HLA class I probe (pHLA-A). Of the 34 restriction fragments detected, 22 were polymorphic. Particular fragments correlated with the presence of HLA-A antigens A1, 2, 3, 10, 11, w19, and 28, but there was little correlation with B antigens. Restriction fragment patterns specific for haemochromatosis were not found with TaqI or during less extensive studies with other restriction enzymes. No differences in restriction fragment patterns were found between four patients and four normal subjects apparently homozygous for HLA-A3 and B7. Examination of Southern blotting patterns for genomic DNA from patients and normal subjects with a panel of 12 restriction enzymes and a probe for the H ferritin gene (pDBR-2) revealed no polymorphisms associated with either idiopathic haemochromatosis or particular HLA phenotypes. These studies provide no support for either HLA class I genes or the H ferritin gene as candidates for the haemochromatosis gene.
 ...
PMID:HLA class I and H ferritin gene polymorphisms in normal subjects and patients with haemochromatosis. 284 58

The serum ferritin concentration was used as a screening test to identify the presence of iron overload in 599 Afrikaans subjects (300 males and 299 females) living in the South Western Cape, South Africa. Seventeen of the males with concentrations greater than 400 micrograms/l were reevaluated three and five years later. Serum ferritin concentrations were measured again and further diagnostic procedures were carried out. These included an assessment of alcohol intake and measurements of serum gamma glutamyltransferase, the percentage saturation of transferrin, and HLA-A,-B,-C, and -DR loci typing on the subjects as well as their families. Liver biopsies were performed on some affected subjects. Of the original 16 index subjects, four were diagnosed as homozygous for the HLA linked iron loading gene which is responsible for the clinical disease idiopathic haemochromatosis. Six appeared to be heterozygotes, three were heterozygotes who were also abusing alcohol, and two did not fit into any of the diagnostic groups. The calculated gene frequency was 0.082, with an expected heterozygote frequency of 0.148. The fact that no females were identified in the study suggested that the diagnostic criteria for homozygosity (serum ferritin greater than 400 micrograms/l and % saturation greater than 60%) were set too high. The data were therefore recalculated for the 300 males; when this was done the gene frequency was 0.115 and the heterozygote frequency 0.024. Two subjects were diagnosed as homozygotes in the study of family members and 37 as heterozygotes (33 definite and four probable). Both the homozygotes and nine of the heterozygotes showed mild to moderate disturbances of iron metabolism. There was considerable overlap between the phenotype expression in these nine heterozygotes and the homozygotes, probably as a result of setting the threshold for the serum ferritin concentrations at the relatively high value of 400 microgram/ml. By doing this a small subset of heterozygotes with biochemical abnormalities was identified. The results of the present pilot study suggest a high frequency of the HLA linked iron loading gene in the Afrikaner population of South Western Cape.
 ...
PMID:The HLA linked iron loading gene in an Afrikaner population. 288 65

A study was carried out to determine the usefulness of erythrocyte ferritin analysis in identifying homozygotes and heterozygotes in families affected with hereditary hemochromatosis, an autosomal recessive disorder. To select the subjects the genotypes of 60 people from 26 affected families were determined by HLA-A and HLA-B haplotyping. In addition, data for 12 homozygotes for whom erythrocyte ferritin values were available from the literature were included. Likelihood analysis was used to evaluate the diagnostic value of erythrocyte ferritin analysis alone and in combination with serum ferritin testing. An erythrocyte ferritin value of 150 ag/cell or higher combined with a serum ferritin level above the 90th percentile indicated homozygosity, whereas a value of less than 150 ag/cell and a serum ferritin level at or below the 90th percentile indicated that homozygosity could be ruled out with a high degree of confidence. The probability of heterozygosity rose to 92% when the erythrocyte ferritin value was between 29 and 149 ag/cell and to 98% when this result was combined with a serum ferritin level at or below the 90th percentile. Erythrocyte ferritin analysis in combination with serum ferritin testing is useful for identifying homozygotes and a proportion of heterozygotes in families affected with hemochromatosis.
 ...
PMID:Usefulness of erythrocyte ferritin analysis in hereditary hemochromatosis. 347 36

HLA-antigens were determined in 21 unrelated patients with idiopathic haemochromatosis and in eight siblings and 13 children of the probands. The prevalences of HLA-A3, B7, and B14 in patients compared to 1967 healthy control subjects were: A3, 76.2% versus 26.9% (p less than 0.0001); B7, 57.1% versus 26.8 (p less than 0.001); B14, 9.5% versus 4.5% (n.s.); A3 and B7, 42.9% versus 12.2% (p less than 0.0001); A3 and B14, 9.5% versus 1.4% (p less than 0.001). Siblings (n = 3) that were HLA-identical with the proband were considered to be homozygotes for the haemochromatosis allele and presented with preclinical haemochromatosis. Siblings and children (n = 17) having only one HLA-haplotype in common with the proband were considered to be heterozygotes. Biochemical markers for haemochromatosis (transferrin saturation and serum ferritin) were higher in homozygous than in heterozygous subjects (p less than 0.0001). The results confirm the association between the HLA-A and B loci and the haemochromatosis gene. HLA-typing is a valuable tool in the identification of the haemochromatosis genotype in a family, and it is an adjunct to the biochemical screening procedure in relatives of patients with this iron overload disorder.
 ...
PMID:HLA determinants in idiopathic haemochromatosis. 405 96

A number of different observations indicate that cells of the immune system can participate in the prevention of potential tissue toxicity from iron accumulation and that, in turn, iron and iron binding proteins have important effects on immune responses. The current studies were undertaken to examine a specific aspect of the interaction of iron with human peripheral blood mononuclear cells. A modified hemolytic plaque-forming assay was used to measure ferritin secretion in vitro by phytohemagglutinin activated or nonactivated mononuclear cells in response to stimulation by ferric citrate. Cells from 55 unrelated healthy subjects collectively representing all well-defined HLA-A, B, C, and DR antigens were studied. There were large reproducible differences in the numbers of plaques formed by different individuals, and there was a statistically significant increase in the frequency of the HLA determinant A3 among the "low" responders. Ferritin secretion measured with an antibody specific for acidic ferritin also showed a distinction between A3 and non-A3 donors. In preliminary cell mixing studies, ferritin secretion by mononuclear cells was shown to require the presence of monocytes and to be influenced by the secretion characteristics of both the monocyte and the T-cell donor. These results may provide a clue to the mechanism of development of idiopathic hemochromatosis which is an HLA-A-linked autosomal recessive disease associated with the specific HLA antigen HLA-A3.
 ...
PMID:Ferritin secretion by human mononuclear cells: association with HLA phenotype. 634 85

Hereditary hemochromatosis is transmitted as an autosomal recessive trait. Analyses of pedigrees suggest that the frequency of disease (proportion of homozygous individuals) in the general population is approximately 0.3% and that approximately 11% of the population are heterozygous. The genotype of 194 persons in 38 pedigrees was determined by HLA-A and HLA-B haplotyping. Likelihood analysis was then used to appraise the transferrin saturation test when used alone and in combination with the serum ferritin test to detect homozygosity and heterozygosity in these pedigrees. A single cut-off point of 55% for transferrin saturation and a cut-off point at the 90th percentile for the serum ferritin level were adequate for the detection of hemochromatosis if homozygosity was considered to be present when the results of one or both tests were positive. To further assess the value of the transferrin saturation test the percentages were stratified into five intervals. A percentage transferrin saturation of 75 or greater and a serum ferritin level above the 90th percentile ruled in homozygosity, whereas a percentage transferrin saturation of less than 55 and a serum ferritin level at or below the 90th percentile ruled it out with confidence. The probability of heterozygosity rose to 90% when the percentage transferrin saturation was between 35 and 55 and the serum ferritin level was at or below the 90th percentile. The use of five cut-off points allowed the probability of homozygosity and heterozygosity in a pedigree to be estimated for all values of transferrin saturation. Although these screening tests are not recommended for use in the general population, they may be worth while in selected groups of patients.
 ...
PMID:Diagnostic efficacy of screening tests for hereditary hemochromatosis. 659 12

The purpose of this pedigree study, comprising 29 families with hereditary haemochromatosis (HH), was to evaluate the relationship between the genotype (G), based on HLA typing, and the phenotype, based on measurement of iron status markers (serum transferrin saturation and serum ferritin). Due to tight linkage between the HH locus and the HLA-A locus, 172 relatives of the 29 unrelated probands could be assigned into three groups: G0 who were considered to be normal (n = 53), G1 who were considered to be heterozygotes (n = 105), and G2 who were considered to be homozygotes (n = 14), according to whether they had no, one or two HLA haplotypes in common with the proband. A high serum transferrin saturation (> 60%) was present in 8/14 = 57.1% of the homozygotes, in 11/105 = 10.5% of the heterozygotes, and in 0/53 = 0% of the normals. Of the homozygotes, 8/14 = 57.1% had preclinical disease, 4/14 = 28.6% had clinically overt iron overload, while 2/14 = 14.3% had normal iron status markers. None of the heterozygotes had clinical evidence of iron overload. Analysis of HLA alleles and iron status markers suggested that 11/105 = 10.5% subjects initially classified as heterozygotes (G1) according to HLA typing should be reclassified as homozygotes because of abnormal iron status markers, explained by either: homozygous x heterozygous (n = 7) or heterozygous x heterozygous (n = 2) matings, HLA recombination (n = 1) or strongly abnormal iron status markers (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Relationship between genotype, assessed by HLA typing, and phenotypic expression of iron status markers in families of 29 probands with hereditary haemochromatosis. 792 65

Genetic (hereditary) hemochromatosis is probably the most common autosomal recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent) are homozygous for the associated gene. The hemochromatosis gene is probably located close to the HLA-A locus on the short arm of chromosome 6. Homozygous individuals may develop severe and potentially lethal hemochromatosis, especially after age 39. Hereditary hemochromatosis involves an increased rate of iron absorption from the gut with subsequent progressive storage of iron in soft organs of the body. Excess iron storage eventually produces pituitary, pancreatic, cardiac, and liver dysfunction and death may result from cardiac arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early diagnosis can prevent these excess iron-induced problems. Iron overload owing to HLA-linked hereditary hemochromatosis can be distinguished from other causes of hemochromatosis by liver biopsies and interpretations. Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations. Family members of hereditary hemochromatosis patients are at increased risk and should be tested. Screening, identification and early treatment (phlebotomies, sometimes in combination with the use of Desferal or other iron-chelating agents) may help prevent or reduce iron-related organ damage and premature deaths. Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.
 ...
PMID:Hereditary hemochromatosis. 978 32


1 2 Next >>