Haemochromatosis and HLA–H

Am, Jouanolle; Gandon, G.; Jézéquel, Pascal; Blayau, Martine; Ml, Campion; Yaouanq, J.; Mosser, Jean; Fergelot, Patricia; Chauvel, Bruno; Bouric, Pascale; Carn, Gwénaëlle; Andrieux, Nancy; Gicquel, Isabelle; Jy, Le Gall; David, M

doi:10.1038/ng1196-251

Cited by 336 publications

(191 citation statements)

References 5 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…This is a new MHC class I-like gene, where homozygosity for a single base pair mutation (C282Y), resulting in a cystein to tyrosine substitution at position 282, was found in 83% of HH patients. This finding was promptly confirmed by other groups who described the presence of the C282Y mutation in varying, but always very high, numbers of hemochro-matosis patients in several parts of the world (Barton et al 1997;Beutler et al 1996;Borot et al 1997;Carella et al 1997;Jazwinska et al 1996;Jouanolle et al 1996). A second mutation was also found in the HFE gene (H63D) resulting in a histidine to aspartic acid substitution at position 63.…”

Section: Introductionsupporting

confidence: 60%

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Porto

Alves²,

Rodrigues³

et al. 1998

Immunogenetics

View full text Add to dashboard Cite

Section: Introductionsupporting

confidence: 60%

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Porto

Alves²,

Rodrigues³

et al. 1998

Immunogenetics

View full text Add to dashboard Cite

“…Some authors suggest that His63Asp could be a polymorphism or a polymorphic marker of another causative mutation of HFE which is different from Cys282Tyr 16,17 ; however, because the two mutations are in complete linkage disequilibrium, an analysis that considers only chromosomes ''at risk,'' i.e., those that do not carry the Cys282Tyr, revealed also that the mutation His63Asp was overrepresented in hemochromatosis and PCT patients, 32 although homozygosity for His63Asp is rare in classic hemochromatosis and the mutation is frequent in normal individuals.…”

Section: Discussionmentioning

confidence: 99%

“…14 A missense mutation of HFE (Cys282Tyr) was reported as tightly associated with the classical hemochromatosis phenotype, which was present in the homozygous state in the large majority of patients of Northern European descent. [14][15][16][17] A second mutation (His63Asp) was also found to have an increased frequency on hemochromatosis chromosomes that did not present with the Cys282Tyr mutation, but its relationship with hemochromatosis has not been clearly established. 14,15 The availability of a genetic marker for hemochromatosis allows for the direct investigation of its relationship with PCT.…”

mentioning

confidence: 99%

High prevalence of the His63Asp HFE mutation in italian patients with porphyria cutanea tarda

et al. 1998

View full text Add to dashboard Cite

Sporadic porphyria cutanea tarda (PCT) is caused by a reduced activity of uroporphyrinogen decarboxylase (URO-D) in the liver. Mild to moderate iron overload is common in PCT, as iron is one of the factors which trigger the clinical manifestations of the disease through the inactivation of URO-D. A role for genetic hemochromatosis in the development of iron overload in sporadic PCT has been hypothesized in the past. The aim of this work was to investigate whether mutations of HFE, which is a candidate gene for hemochromatosis, play the role of genetic susceptibility factors for PCT in Italian patients, who have a high prevalence of acquired triggering factors, such as hepatitis C virus (HCV) chronic infection and alcohol. We determined HFE genotypes of 68 male patients with PCT. Our data do not confirm an association of PCT with the Cys282Tyr HFE mutation, strongly associated with hemochromatosis in Northern European countries. A second mutation of HFE, His63Asp, however, had a significantly increased frequency as it was present in half of the patients. Surprisingly, the presence of the His63Asp mutation was not related to the iron status of patients, suggesting that a subtle abnormality of iron metabolism induced by this mutation could escape detection by the standard parameters of iron status. In PCT patients with liver disease, the presence of the mutation could contribute to the inactivation of URO-D, either directly or through a synergistic action with other factors that cause liver damage. (HEPATOLOGY 1998;27;181-184.)

show abstract

“…It has been suggested that other genetic and environmental factors might contribute to the modulation of iron metabolism. [33][34][35][36] In the more severe cases of iron overload, abnormally low numbers of lymphocytes, especially CD8 + T cells, remain a valuable indicator for disease prognosis. 37,38 This, in conjunction with the finding that the class I-like HFE molecule is encoded in the MHC, strongly suggest that an interplay between iron metabolism and immune function must exist.…”

Section: Discussionmentioning

confidence: 99%

The major histocompatibility complex-encoded class I-like HFE abrogates endocytosis of transferrin receptor by inducing receptor phosphorylation

Salter–Cid¹,

Brunmark²,

Peterson³

et al. 2000

Genes Immun

View full text Add to dashboard Cite

The major histocompatibility complex-encoded gene, Hfe, has been implicated to play a pivotal role in hereditary hemochromatosis, a common autosomal recessive disorder of iron metabolism. The recent finding that a physical interaction between HFE and transferrin receptor establishes a functional link between HFE and transferrin receptormediated iron metabolism in the pathophysiology of hereditary hemochromatosis. To elucidate the underlying mechanisms by which HFE interacts with and affects transferrin receptor function, we have systematically investigated the consequences of the HFE-transferrin receptor interaction in cellular iron homeostasis. Herein we show that in HFEexpressing cells, the amount of intracellular transferrin is decreased by ෂ28%, despite a ෂ40% increase in surfaceexpressed transferrin receptor. Kinetic analysis of receptor-bound transferrin endocytosis reveals that HFE expression not only reduces transferrin binding but also abrogates transferrin receptor endocytosis. As a result, HFE expression leads to an accumulation of non-functional transferrin receptors at the cell surface, and a decrease in iron uptak. Moreover, HFE expression induces hyper-serine phosphorylation of the transferrin receptor. Taken together, these results suggest that HFE negatively modulates cellular iron uptake by impairing transferrin receptor endocytosis via HFE-induced receptor phosphorylation. Genes and Immunity (2000) 1, 409-417.

show abstract

Haemochromatosis and HLA–H

Cited by 336 publications

References 5 publications

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

High prevalence of the His63Asp HFE mutation in italian patients with porphyria cutanea tarda

The major histocompatibility complex-encoded class I-like HFE abrogates endocytosis of transferrin receptor by inducing receptor phosphorylation

Contact Info

Product

Resources

About