HFE Gene Polymorphisms and the Risk for Autism in Egyptian Children and Impact on the Effect of Oxidative Stress

Background: Autism is among the commonest neurodevelopmental childhood disorders worldwide; its aetiology is still unknown. Iron metabolism alteration in the central nervous system is recently implicated as a risk factor for several neurodegenerative disorders.Haemochromatosis HFE gene polymorphisms (p.H63D and p.C282Y) have shown significant association with several neurological diseases. Some evidences show altered iron related proteins in serum of autistic children. The aim of this work is to conduct a preliminary pilot study for the association of HFE polymorphisms and autism.Methods: All cases were referred from the clinic of special needs, National Research Centre, Cairo. Clinical diagnosis was based on the criteria for autistic disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR).Whole genome DNA was extracted; p.H63D and p.C282Y genotyping was studied using specific sequence amplification followed by restriction enzyme digestion on a sample of autism patients (25 cases) and twenty controls.Results: The p.H63D is more abundant than the C282Y among both autism and control samples. No significant association of p.H63D nor p.C282Y polymorphism and autism was revealed.Conclusion: We here report on the first pilot study of the possible genetic association between autism and HFE gene polymorphisms among Egyptians. Although our results do not prove the role of HFE polymorphisms as risk factors for autism, yet this does not exclude the role of iron in this prevalent disorder. Further extended studies are recommended to include other iron metabolism genes.

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Iron metabolism and the role of HFE gene polymorphisms in Wilson disease

Liver International ◽

10.1111/j.1478-3231.2011.02661.x ◽

2011 ◽

Vol 32 (1) ◽

pp. 165-170 ◽

Cited By ~ 26

Author(s):

Jan Pfeiffenberger ◽

Daniel N. Gotthardt ◽

Thomas Herrmann ◽

Jessica Seeßle ◽

Uta Merle ◽

...

Keyword(s):

Iron Metabolism ◽

Wilson Disease ◽

Gene Polymorphisms ◽

Hfe Gene

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Role of vitamin D in iron metabolism, a pilot study

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20150735 ◽

2015 ◽

pp. 1494-1498 ◽

Cited By ~ 1

Author(s):

Uma Pandey ◽

Hema Divakar

Keyword(s):

Vitamin D ◽

Pilot Study ◽

Iron Metabolism

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Role of BLMH, XPO5 and HFE gene polymorphisms in Hodgkin lymphoma susceptibility in the South Indian population

Annals of Oncology ◽

10.1093/annonc/mdx664.013 ◽

2017 ◽

Vol 28 ◽

pp. x98

Author(s):

D. Thakkar

Keyword(s):

Hodgkin Lymphoma ◽

Gene Polymorphisms ◽

Indian Population ◽

Hfe Gene ◽

South Indian Population ◽

The South ◽

South Indian

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Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation

Blood ◽

10.1182/blood-2003-03-0672 ◽

2003 ◽

Vol 102 (3) ◽

pp. 783-788 ◽

Cited By ~ 890

Author(s):

Tomas Ganz

Keyword(s):

Iron Overload ◽

Iron Metabolism ◽

Negative Regulator ◽

Hfe Gene ◽

Iron Release ◽

Nonsense Mutations ◽

Amino Acid Peptide ◽

Juvenile Hemochromatosis ◽

Anemia Of Inflammation

Abstract Human hepcidin, a 25–amino acid peptide made by hepatocytes, may be a new mediator of innate immunity and the long-sought iron-regulatory hormone. The synthesis of hepcidin is greatly stimulated by inflammation or by iron overload. Evidence from transgenic mouse models indicates that hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron transport across the placenta, and iron release from macrophages. The key role of hepcidin is confirmed by the presence of nonsense mutations in the hepcidin gene, homozygous in the affected members, in 2 families with severe juvenile hemochromatosis. Recent evidence shows that deficient hepcidin response to iron loading may contribute to iron overload even in the much milder common form of hemochromatosis, from mutations in the HFE gene. In anemia of inflammation, hepcidin production is increased up to 100-fold and this may account for the defining feature of this condition, sequestration of iron in macrophages. The discovery of hepcidin and its role in iron metabolism could lead to new therapies for hemochromatosis and anemia of inflammation.

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Role of Ferroportin in Macrophage-Mediated Immunity

Infection and Immunity ◽

10.1128/iai.00498-10 ◽

2010 ◽

Vol 78 (12) ◽

pp. 5099-5106 ◽

Cited By ~ 45

Author(s):

Erin E. Johnson ◽

Andreas Sandgren ◽

Bobby J. Cherayil ◽

Megan Murray ◽

Marianne Wessling-Resnick

Keyword(s):

Immune Responses ◽

Iron Metabolism ◽

Host Response ◽

Inhibitory Effect ◽

Hfe Gene ◽

Inos Mrna ◽

No Production ◽

Transferrin Receptors ◽

Histocompatibility Complex

ABSTRACT Perturbations in iron metabolism have been shown to dramatically impact host response to infection. The most common inherited iron overload disorder results from defects in the HFE gene product, a major histocompatibility complex class I-like protein that interacts with transferrin receptors. HFE-associated hemochromatosis is characterized by abnormally high levels of the iron efflux protein ferroportin. In this study, J774 murine macrophages overexpressing ferroportin were used to investigate the influence of iron metabolism on the release of nitric oxide (NO) in response to infection. Overexpression of ferroportin significantly impaired intracellular Mycobacterium tuberculosis growth during early stages of infection. When challenged with lipopolysaccharide (LPS) or M. tuberculosis infection, control macrophages increased NO synthesis, but macrophages overexpressing ferroportin had significantly impaired NO production in response to LPS or M. tuberculosis. Increased NO synthesis in control cells was accompanied by increased iNOS mRNA and protein, while upregulation of iNOS protein was markedly reduced when J744 cells overexpressing ferroportin were challenged with LPS or M. tuberculosis, thus limiting the bactericidal activity of these macrophages. The proinflammatory cytokine gamma interferon reversed the inhibitory effect of ferroportin overexpression on NO production. These results suggest a novel role for ferroportin in attenuating macrophage-mediated immune responses.

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Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20200089 ◽

2020 ◽

Vol 78 (8) ◽

pp. 494-500 ◽

Cited By ~ 4

Author(s):

Adalberto STUDART-NETO ◽

Bruno Fukelmann GUEDES ◽

Raphael de Luca e TUMA ◽

Antonio Edvan CAMELO FILHO ◽

Gabriel Taricani KUBOTA ◽

...

Keyword(s):

Neurological Diseases ◽

Neuromuscular Disorders ◽

Neurological Symptoms ◽

University Hospital ◽

Special Treatment ◽

Nasal Swabs ◽

Neurological Exam ◽

Neurological Conditions ◽

De Medicina

ABSTRACT Background: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

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