Search results for "Hemochromatosis Protein"

High HFE mutation incidence in idiopathic erythrocytosis.

2018

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population.

2001

Classes I and II human leukocyte antigens (HLA) genes encode highly polymorphic heterodimeric glycoproteins involved in the control of immune responses. The HLA class I gene HFE seemingly no longer participates in immunity because it has lost its ability to bind peptides and it has acquired the ability to form complex with the receptor for iron-binding transferrin by regulating iron uptake by intestinal cells. Thus, it indirectly regulates immune responses too, because iron availability plays a role in specific and non-specific immune responses. The distribution of HFE polymorphisms in Sicilian centenarians and nonagenarians was studied to evaluate if HFE alleles might be represented differ…

Association between HFE mutations and acute myocardial infarction: a study in patients from Northern and Southern Italy.

2003

There is interest in the role of iron in age-related diseases such as atherosclerosis. Tissue iron deposition could be harmful, because Fe(2+) can react with H(2)O(2) to form OH(-) radicals and Fe(2+) can react with O(2) to form reactive oxygen species. Free radicals react with cell membranes and cell organelles and could lead to the development of atherosclerosis by initiating lipid peroxidation. Hereditary hemochromatosis provides an opportunity for studying the effects of iron on cardiovascular disease. Some studies have shown that individuals who carried HFE mutations may be at greater risk of developing coronary heart disease than those without the mutations. In contrast, a large numbe…

Increased p53 mutation load in nontumorous human liver of Wilson disease and hemochromatosis: Oxyradical overload diseases

2000

Hemochromatosis and Wilson disease (WD), characterized by the excess hepatic deposition of iron and copper, respectively, produce oxidative stress and increase the risk of liver cancer. Because the frequency of p53 mutated alleles in nontumorous human tissue may be a biomarker of oxyradical damage and identify individuals at increased cancer risk, we have determined the frequency of p53 mutated alleles in nontumorous liver tissue from WD and hemochromatosis patients. When compared with the liver samples from normal controls, higher frequencies of G:C to T:A transversions at codon 249 ( P < 0.001) and C:G to A:T transversions and C:G to T:A transitions at codon 250 ( P < 0.001 and P &…

Frequency of the HFE Gene Mutations in Five Italian Populations

2002

Abstract ABSTRACT Genetic hemochromatosis is an autosomal recessive disorder characterized by iron overload and a variety of clinical manifestations such as liver cirrhosis and arthropathy. It is the most common genetic disease of northern European populations. The principal gene responsible for hereditary hemochromatosis, designated HFE, is located on chromosome 6 in the HLA region. The single point mutation 845A, changing cysteine at position 282 to tyrosine (C282Y), in this gene has been identified as the main genetic basis of hereditary hemochromatosis. Two other mutations, 187G, a histidine to aspartate at amino acid 63 (H63D), and 193T, a serine to cysteine at amino acid 65 (S65C), ap…

A new polymorphism in the human HFE gene

1999

HFE p.H63D polymorphism does not influence ALS phenotype and survival.

2015

It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significa…

Association between the HFE mutations and unsuccessful ageing: a study in Alzheimer's disease patients from Northern Italy

2003

Mutations in the class I-like Major Histocompatibility Complex gene HFE are associated with hereditary hemochromatosis (HH), a disorder caused by excessive iron uptake. Three common mutations have been found: C282Y, H63D, and S65C. Moreover, several studies have suggested that HFE mutations may be involved in several age-related chronic diseases such as Alzheimer's disease (AD) and coronary heart disease, but apparently paradoxically also with longevity. In particular, in AD, patients carrying the H63D allele have been suggested to have a mean age at onset of 72 vs. 77 years for those who were homozygous for the wild-type allele. Thus, it seems that H63D mutations may anticipate sporadic AD…

Association between the HFE mutations and longevity: a study in Sardinian population

2003

Hereditary hemochromatosis is an HLA-linked inherited disease characterised by inappropriately high absorption of iron by the gastrointestinal mucosa. The cysteine-to-tyrosine substitution at codon 282 of the HFE encoding gene sequence is responsible for the disease, although other variants, as H63D and S65C, may modify the affinity of the protein for transferrin receptors. We have recently reported that C282Y mutation is significantly increased in very old (>90 years) Sicilian women, suggesting a role in attainment of longevity. In addition, an increase of H63D polymorphism was also observed in these women but the difference was not significant. To validate and extend these results we inve…

Mutations in the HFE gene and cardiovascular disease risk: an individual patient data meta-analysis of 53 880 subjects.

2008

Background— Whether mutations in the hemochromatosis (HFE) gene increase cardiovascular disease risk is still undetermined. The main reason is the low frequency of the mutations, in particular of the compound C282Y/H63D genotype. We combined the data of 11 observational studies for an individual patient data meta-analysis. Methods and Results— Individual patient data were obtained from published as well as unpublished studies that had information available on the C282Y mutation as well as the H63D mutation in relation to coronary heart disease risk. Individual records were provided on each of the 53 880 participants in 11 studies. In total, 10 541 patients with coronary events were documen…