Pathophysiological consequences and benefits of
            <i>HFE</i>
            mutations: 20 years of research

Hollerer, Ina; Bachmann, André; Muckenthaler, Martina U.

doi:10.3324/haematol.2016.160432

Cited by 56 publications

(59 citation statements)

References 120 publications

(139 reference statements)

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“…Moreover, both at diagnosis and after a GFD, the celiac patients with H63D mutation, that is, non‐IDA subjects, showed higher hemoglobin and serum iron than those with the wild‐type HFE genotype. Large‐scale population studies have revealed that most HFE mutation carriers with a mild iron overload‐phenotype lack any clinically relevant disease symptoms, leading to the hypothesis that HFE mutations may confer a genetic advantage on asymptomatic hemochromatosis “patients” and have, therefore, continued to spread . The C282Y variant is considered to play the most important role in iron metabolism.…”

Section: Discussionmentioning

confidence: 99%

The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease

et al. 2017

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We investigated the role of HFE C282Y, H63D, and TMPRSS6 A736V variants in the pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at diagnosis and after 1 year of gluten-free diet (GFD). Demographic and clinical features were prospectively recorded for all CD patients between 2013 and 2017. C282Y, H63D, and A736V variants were evaluated for CD patients and controls. Finally, 505 consecutive CD patients and 539 age-matched control subjects were enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele frequency was significantly increased in CD compared with controls (1.1% vs 0.2%, P = .001), whereas H63D and A736V allele frequencies were similar among patients and controls (P = .92 and .84, respectively). At diagnosis, C282Y variant in anemic CD patients was significantly increased compared to nonanemic group (2% and 0.5%, P = .04). At follow-up, A736V was significantly increased in IDA persistent than in IDA not persistent (57.7% vs 35.2%, P < .0001). CD patients with H63D mutation showed higher Hb, MCV, serum iron, and ferritin levels than subjects without HFE mutations. Decreased hepcidin values were observed in anemic compared to nonanemic subjects at follow-up (1.22 ± 1.14 vs 2.08 ± 2.15, P < .001). This study suggests a protective role of HFE in IDA CD patients and confirms the role of TMPRSS6 in predicting oral iron response modulating hepcidin action on iron absorption. Iron supplementation therapeutic management in CD could depend on TMPRSS6 genotype that could predict persistent IDA despite iron supplementation and GFD.

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Section: Discussionmentioning

confidence: 99%

The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease

et al. 2017

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“…Während die C282Y-Mutation in Nord-und Mitteleuropa häufig vorkommt, findet sie sich bei südeuropäischen Völkern deutlich seltener und außerhalb Europas nur sehr selten [3]. Aufgrund der geringen Penetranz sowie der geografischen Variabilität werden evolutionäre Vorteile durch die Mutationen diskutiert [4]. Die nicht das HFE-Gen betreffenden Formen II-IV sind deutlich seltener und betreffen im Gegensatz zu Typ I auch nicht europäische Menschen aller Altersgruppen [5].…”

Section: Genetikunclassified

“…Ist dessen Bindungskapazität erschöpft, wird das nicht transferringebundene Eisen vermehrt von Organen wie Leber und Pankreas, aber auch vom Herzen aufgenommen. Die typischen Organdysfunktionen sind Folge der Akkumulation freien intrazellulären Eisens und der Bildung von OH-Radikalen [4].…”

Section: Symptomatikunclassified

Hereditäre Hämochromatose und Blutspende: Patient oder Spender?

Deitenbeck

Zeiler

2018

Transfusionsmedizin

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ZusammenfassungBei der hereditären Hämochromatose (HH) handelt es sich um eine genetisch bedingte Störung des Eisenstoffwechsels, die bei der Mehrzahl der Betroffenen zu einer Verminderung von Hepcidin führt, das durch Bindung an Ferroportin im Darm die Resorption von Eisen hemmt. Hieraus resultieren Eisenablagerungen in verschiedenen Organen. Die Therapie besteht in der Entfernung von in Hämoglobin gebundenem Eisen durch regelmäßigen Aderlass, weshalb Blutspenden den Krankheitsverlauf positiv beeinflussen.

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“…4) [112][113][114]. Hepatic dysfunction indicated by elevations of serum alanine aminotransferase levels is often observed in the relatively early stages of this disease.…”

Section: Manifestations Of Hhmentioning

confidence: 99%

“…The very high incidences of mutations in the HFE gene among Caucasians evoke the idea that these mutations might have offered advantages to their carriers [114]. For instance, increased iron uptake might have offered advantages to people with a grain-based diet and especially to women of reproductive ages in their survival and reproduction.…”

Section: Evolutional Benefits Of Hfe Mutationsmentioning

confidence: 99%

The mechanisms of systemic iron homeostasis and etiology, diagnosis, and treatment of hereditary hemochromatosis

Kawabata

2017

Int J Hematol

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Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders that manifest with various symptoms, including hepatic dysfunction, diabetes, and cardiomyopathy. Classic HH type 1, which is common in Caucasians, is caused by bi-allelic mutations of HFE. Severe types of HH are caused by either bi-allelic mutations of HFE2 that encodes hemojuvelin (type 2A) or HAMP that encodes hepcidin (type 2B). HH type 3, which is of intermediate severity, is caused by bi-allelic mutations of TFR2 that encodes transferrin receptor 2. Mutations of SLC40A1 that encodes ferroportin, the only cellular iron exporter, causes either HH type 4A (loss-of-function mutations) or HH type 4B (gain-of-function mutations). Studies on these gene products uncovered a part of the mechanisms of the systemic iron regulation; HFE, hemojuvelin, and TFR2 are involved in iron sensing and stimulating hepcidin expression, and hepcidin downregulates the expression of ferroportin of the target cells. Phlebotomy is the standard treatment for HH, and early initiation of the treatment is essential for preventing irreversible organ damage. However, because of the rarity and difficulty in making the genetic diagnosis, a large proportion of patients with non-HFE HH might have been undiagnosed; therefore, awareness of this disorder is important.

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Pathophysiological consequences and benefits of HFE mutations: 20 years of research

Cited by 56 publications

References 120 publications

The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease

The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease

Hereditäre Hämochromatose und Blutspende: Patient oder Spender?

The mechanisms of systemic iron homeostasis and etiology, diagnosis, and treatment of hereditary hemochromatosis

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