HFE

Summary

Gene Symbol: HFE
Description: homeostatic iron regulator
Alias: HFE1, HLA-H, MVCD7, TFQTL2, hereditary hemochromatosis protein, MHC class I-like protein HFE, hereditary hemochromatosis protein HLA-H, high Fe
Species: human
Products:     HFE

Top Publications

  1. Aguilar Martinez P, Grandchamp B, Cunat S, Cadet E, Blanc F, Nourrit M, et al. Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants. Haematologica. 2011;96:507-14 pubmed publisher
    Heterozygotes for the p.Cys282Tyr (C282Y) mutation of the HFE gene do not usually express a hemochromatosis phenotype. Apart from the compound heterozygous state for C282Y and the widespread p...
  2. Allen K, Bertalli N, Osborne N, Constantine C, Delatycki M, Nisselle A, et al. HFE Cys282Tyr homozygotes with serum ferritin concentrations below 1000 microg/L are at low risk of hemochromatosis. Hepatology. 2010;52:925-33 pubmed publisher
    Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is a genetic predisposition to iron overload and subsequent signs and symptoms of disease that potentially affects approximately 80,000 persons in Australia and almost ..
  3. Gannon P, Medelci S, Le Page C, Beaulieu M, Provencher D, Mes Masson A, et al. Impact of hemochromatosis gene (HFE) mutations on epithelial ovarian cancer risk and prognosis. Int J Cancer. 2011;128:2326-34 pubmed publisher
    ..Cellular iron uptake is regulated by the transferrin receptor and the hemochromatosis protein (HFE) system...
  4. Pedersen P, Milman N. Extrinsic factors modifying expressivity of the HFE variant C282Y, H63D, S65C phenotypes in 1,294 Danish men. Ann Hematol. 2009;88:957-65 pubmed publisher
    This study analysed the influence of extrinsic factors on the phenotypic expression of HFE gene variants in ethnic Danish men. A cohort of 6,020 men aged 30-53 years was screened for HFE C282Y, H63D and S65C variants...
  5. Gray S, Crowe J, Lawless M. Hemochromatosis: as a conformational disorder. Int J Biochem Cell Biol. 2009;41:2094-7 pubmed publisher
    ..overload syndromes that includes the disorder related to C282Y homozygous mutation of the hemochromatosis protein (HFE), the most common form of hereditary hemochromatosis...
  6. Cançado R, Guglielmi A, Vergueiro C, Rolim E, Figueiredo M, Chiattone C. Analysis of HFE gene mutations and HLA-A alleles in Brazilian patients with iron overload. Sao Paulo Med J. 2006;124:55-60 pubmed
    ..The objective was to analyze the presence of C282Y, H63D and S65C mutations in the HFE gene and HLA-A alleles for a group of Brazilian patients with iron overload, and to correlate genotype with ..
  7. Restagno G, Lombardo F, Ghiglione P, Calvo A, Cocco E, Sbaiz L, et al. HFE H63D polymorphism is increased in patients with amyotrophic lateral sclerosis of Italian origin. J Neurol Neurosurg Psychiatry. 2007;78:327 pubmed
  8. Cukjati M, Vaupotic T, Rupreht R, Curin Serbec V. Prevalence of H63D, S65C and C282Y hereditary hemochromatosis gene mutations in Slovenian population by an improved high-throughput genotyping assay. BMC Med Genet. 2007;8:69 pubmed
    ..Although the most prevalent genotype in HH is homozygosity for C282Y mutation of the HFE gene, two additional mutations, H63D and S65C, appear to be associated with a milder form of HH...
  9. Santos P, Cançado R, Terada C, Rostelato S, Gonzales I, Hirata R, et al. HFE gene mutations and iron status of Brazilian blood donors. Braz J Med Biol Res. 2010;43:107-14 pubmed
    Mutations of the HFE and TFR2 genes have been associated with iron overload. HFE and TFR2 mutations were assessed in blood donors, and the relationship with iron status was evaluated...

More Information

Publications88

  1. Gao J, Chen J, Kramer M, Tsukamoto H, Zhang A, Enns C. Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metab. 2009;9:217-27 pubmed publisher
    ..Patients with the most common form of hereditary iron overload have mutations in the hereditary hemochromatosis protein HFE. They have lower levels of hepcidin than unaffected individuals...
  2. Park S, Hu H, Wright R, Schwartz J, Cheng Y, Sparrow D, et al. Iron metabolism genes, low-level lead exposure, and QT interval. Environ Health Perspect. 2009;117:80-5 pubmed publisher
    ..enhance the oxidative effects of lead, we examined whether polymorphisms in iron metabolism genes [hemochromatosis (HFE), transferrin (TF) C2, and heme oxygenase-1 (HMOX-1)] increase susceptibility to the effects of lead on QT interval ..
  3. Rossetti M, Mendez M, Afonso S, Gerez E, Batlle A, Munoz A, et al. HFE gene mutations in patients with altered iron metabolism in Argentina. Cell Mol Biol (Noisy-le-grand). 2009;55:31-5 pubmed
    ..HH Type I is inherited as an autosomal recessive trait of mutations in HFE gene...
  4. Praline J, Blasco H, Vourc H P, Rat V, Gendrot C, Camu W, et al. Study of the HFE gene common polymorphisms in French patients with sporadic amyotrophic lateral sclerosis. J Neurol Sci. 2012;317:58-61 pubmed publisher
    Our objective was to investigate whether the C282Y (p.Cys 282 Tyr) and H63D (p. His 63 Asp) HFE polymorphisms were associated with sporadic amyotrophic lateral sclerosis (SALS) in the French population...
  5. Constantine C, Anderson G, Vulpe C, McLaren C, Bahlo M, Yeap H, et al. A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis. Br J Haematol. 2009;147:140-9 pubmed publisher
    There is emerging evidence that there are genetic modifiers of iron indices for HFE gene mutation carriers at risk of hereditary hemochromatosis...
  6. Rochette J, Le Gac G, Lassoued K, Ferec C, Robson K. Factors influencing disease phenotype and penetrance in HFE haemochromatosis. Hum Genet. 2010;128:233-48 pubmed publisher
    Haemochromatosis is predominantly associated with the HFE p.C282Y homozygous genotype, which is present in approximately 1 in 200 people of Northern European origin. However, not all p...
  7. Lee S, Patton S, Henderson R, Connor J. Consequences of expressing mutants of the hemochromatosis gene (HFE) into a human neuronal cell line lacking endogenous HFE. FASEB J. 2007;21:564-76 pubmed
    b>HFE mutations have traditionally been associated with the iron overload disorder known as hemochromatosis...
  8. Carroll G. HFE gene mutations are associated with osteoarthritis in the index or middle finger metacarpophalangeal joints. J Rheumatol. 2006;33:741-3 pubmed
    To test the hypothesis that possession of either C282Y or H63D mutations in the HFE gene is associated with primary osteoarthritis (OA) in joints commonly affected in hemochromatotic arthropathy...
  9. Gurrin L, Bertalli N, Dalton G, Osborne N, Constantine C, McLaren C, et al. HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity. Hepatology. 2009;50:94-101 pubmed publisher
    The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D)...
  10. Solanas Barca M, Mateo Gallego R, Calmarza P, Jarauta E, Bea A, Cenarro A, et al. Mutations in HFE causing hemochromatosis are associated with primary hypertriglyceridemia. J Clin Endocrinol Metab. 2009;94:4391-7 pubmed publisher
    ..The aim of the study was to analyze whether HFE mutations causing hereditary hemochromatosis (HH) are associated with primary HTG...
  11. Baja E, Schwartz J, Wellenius G, Coull B, Zanobetti A, Vokonas P, et al. Traffic-related air pollution and QT interval: modification by diabetes, obesity, and oxidative stress gene polymorphisms in the normative aging study. Environ Health Perspect. 2010;118:840-6 pubmed publisher
    ..Traffic-related pollutants may increase QTc among persons with diabetes, persons who are obese, and nonsmoking elderly individuals; the number of genetic variants related to oxidative stress increases this effect. ..
  12. Adams P, Pankow J, Barton J, Acton R, Leiendecker Foster C, McLaren G, et al. HFE C282Y homozygosity is associated with lower total and low-density lipoprotein cholesterol: The hemochromatosis and iron overload screening study. Circ Cardiovasc Genet. 2009;2:34-7 pubmed publisher
    ..primary care from 5 field centers in the United States and Canada with serum ferritin, transferrin saturation, and HFE genotyping for C282Y and H63D mutations...
  13. Mariani R, Pelucchi S, Arosio C, Coletti S, Pozzi M, Paolini V, et al. Genetic and metabolic factors are associated with increased hepatic iron stores in a selected population of p.Cys282Tyr heterozygotes. Blood Cells Mol Dis. 2010;44:159-63 pubmed publisher
    ..associated with a hemochromatosis phenotype, unless associated in the compound heterozygous state with other HFE mutations...
  14. Raszeja Wyszomirska J, Kurzawski G, Suchy J, Zawada I, Lubinski J, Milkiewicz P. Frequency of mutations related to hereditary haemochromatosis in northwestern Poland. J Appl Genet. 2008;49:105-7 pubmed publisher
    Hereditary haemochromatosis has been linked with C282Y and H63D mutations of the HFE gene. In Europe, frequencies of these mutations are the highest in Northern European countries and gradually decrease southwards...
  15. Benyamin B, McRae A, Zhu G, Gordon S, Henders A, Palotie A, et al. Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels. Am J Hum Genet. 2009;84:60-5 pubmed publisher
    ..found two additional and independent SNPs on TF (rs1799852 and rs2280673) and confirmed the known C282Y mutation in HFE to be independently associated with serum transferrin...
  16. Wang F, Hu H, Schwartz J, Weuve J, Spiro A, Sparrow D, et al. Modifying effects of the HFE polymorphisms on the association between lead burden and cognitive decline. Environ Health Perspect. 2007;115:1210-5 pubmed
    As iron and lead promote oxidative damage, and hemochromatosis (HFE) gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship.
  17. Toll A, Celis R, Ozalla M, Bruguera M, Herrero C, Ercilla M. The prevalence of HFE C282Y gene mutation is increased in Spanish patients with porphyria cutanea tarda without hepatitis C virus infection. J Eur Acad Dermatol Venereol. 2006;20:1201-6 pubmed
    ..On the other hand, the prevalence of the H63D mutation seems not to be increased in patients with PCT. The possibility of an association between HCV infection and H63D mutation in inducing PCT can be hypothesized. ..
  18. Milet J, Dehais V, Bourgain C, Jouanolle A, Mosser A, Perrin M, et al. Common variants in the BMP2, BMP4, and HJV genes of the hepcidin regulation pathway modulate HFE hemochromatosis penetrance. Am J Hum Genet. 2007;81:799-807 pubmed
    Most cases of genetic hemochromatosis (GH) are associated with the HFE C282Y/C282Y (p.Cys282Tyr/p.Cys282Tyr) genotype in white populations. The symptoms expressed by C282Y homozygotes are extremely variable...
  19. Chen J, Chloupkova M, Gao J, Chapman Arvedson T, Enns C. HFE modulates transferrin receptor 2 levels in hepatoma cells via interactions that differ from transferrin receptor 1-HFE interactions. J Biol Chem. 2007;282:36862-70 pubmed
    Mutations in the transmembrane glycoproteins transferrin receptor 2 (TfR2) and HFE are associated with hereditary hemochromatosis...
  20. van der A D, Peeters P, Grobbee D, Roest M, Marx J, Voorbij H, et al. HFE mutations and risk of coronary heart disease in middle-aged women. Eur J Clin Invest. 2006;36:682-90 pubmed
    Although heterozygosity for the C282Y mutation in the HFE gene has been associated with an increased risk of cardiovascular events, epidemiological studies remain inconclusive...
  21. Pankow J, Boerwinkle E, Adams P, Guallar E, Leiendecker Foster C, Rogowski J, et al. HFE C282Y homozygotes have reduced low-density lipoprotein cholesterol: the Atherosclerosis Risk in Communities (ARIC) Study. Transl Res. 2008;152:3-10 pubmed publisher
    Recent studies have raised questions about the long-term health risks for individuals with mutations in the HFE gene, although previous studies may have been plagued by selection bias or lack of population-based comparison groups...
  22. Aranda N, Viteri F, Montserrat C, Arija V. Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain. Ann Hematol. 2010;89:767-73 pubmed publisher
    Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption...
  23. Dunn T, Blankenship D, Beal N, Allen R, Schechter E, Moore W, et al. HFE mutations in heart disease. Heart Vessels. 2008;23:348-55 pubmed publisher
    ..the reported association of cardiac complications with hereditary hemochromatosis and the high carrier frequency of HFE gene mutations in the natural population, it seems reasonable that such mutations might appear more frequently than ..
  24. Mitchell R, Lee S, Randazzo W, Simmons Z, Connor J. Influence of HFE variants and cellular iron on monocyte chemoattractant protein-1. J Neuroinflammation. 2009;6:6 pubmed publisher
    Polymorphisms in the MHC class 1-like gene known as HFE have been proposed as genetic modifiers of neurodegenerative diseases that include neuroinflammation as part of the disease process...
  25. Park S, O Neill M, Wright R, Hu H, Vokonas P, Sparrow D, et al. HFE genotype, particulate air pollution, and heart rate variability: a gene-environment interaction. Circulation. 2006;114:2798-805 pubmed
    ..The protein product of the hemochromatosis (HFE) gene modulates uptake of iron and divalent cations from pulmonary sources and reduces their toxicity...
  26. Osborne N, Gurrin L, Allen K, Constantine C, Delatycki M, McLaren C, et al. HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology. 2010;51:1311-8 pubmed publisher
    The evidence that mutations in the HFE gene for hemochromatosis are associated with increased cancer risk is inconsistent. The Melbourne Collaborative Cohort Study is a prospective cohort study that commenced recruitment in 1990...
  27. Walsh A, Dixon J, Ramm G, Hewett D, Lincoln D, Anderson G, et al. The clinical relevance of compound heterozygosity for the C282Y and H63D substitutions in hemochromatosis. Clin Gastroenterol Hepatol. 2006;4:1403-10 pubmed
    Two major mutations are defined within the hemochromatosis gene, HFE. Although the effects of the C282Y substitution have been well characterized, the clinical significance of the C282Y/H63D state remains unclear...
  28. Acton R, Barton J, Passmore L, Adams P, Speechley M, Dawkins F, et al. Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes in the Hemochromatosis and Iron Overload Screening (HEIRS) study. Diabetes Care. 2006;29:2084-9 pubmed
    ..the associations of self-reported diabetes with serum ferritin concentration, transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five field centers in the Hemochromatosis and ..
  29. Voicu P, Cojocariu C, Petrescu Danila E, Covic M, Stanciu C, Rusu M. Prevalence of HFE (hemochromatosis) gene mutations C282Y and H63D in a Romanian population. Blood Cells Mol Dis. 2009;42:14-5 pubmed publisher
  30. Dorak M, Mackay R, Relton C, Worwood M, Parker L, Hall A. Hereditary hemochromatosis gene (HFE) variants are associated with birth weight and childhood leukemia risk. Pediatr Blood Cancer. 2009;53:1242-8 pubmed publisher
    Our original studies reported an association between the iron-metabolism gene HFE and risk of childhood acute lymphoblastic leukemia (ALL), and a birth weight association in ALL...
  31. Guerreiro R, Bras J, Santana I, Januario C, Santiago B, Morgadinho A, et al. Association of HFE common mutations with Parkinson's disease, Alzheimer's disease and mild cognitive impairment in a Portuguese cohort. BMC Neurol. 2006;6:24 pubmed
    ..Iron metabolism is associated with the gene hemochromatosis (HFE Human genome nomenclature committee ID:4886), and mutations in HFE are a cause of the iron mismetabolism disease, ..
  32. Ellervik C, Tybjaerg Hansen A, Appleyard M, Sillesen H, Boysen G, Nordestgaard B. Hereditary hemochromatosis genotypes and risk of ischemic stroke. Neurology. 2007;68:1025-31 pubmed
    We tested the hypothesis that the HFE genotypes H63D/H63D, H63D/wild type, C282Y/H63D, C282Y/C282Y, and C282Y/wild type are risk factors for symptomatic carotid atherosclerosis, ischemic cerebrovascular disease (ICVD), and ischemic ..
  33. van Rheenen W, Diekstra F, van Doormaal P, Seelen M, Kenna K, McLaughlin R, et al. H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis. Neurobiol Aging. 2013;34:1517.e5-7 pubmed publisher
    The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS...
  34. Wolff C, Armas R, Frank J, Poblete P. [Mutations of hemochromatosis gene in volunteer blood donors and Chilean porphyria cutanea tarda patients]. Medicina (B Aires). 2006;66:421-6 pubmed
    ..The H63D and C282Y mutations of the HFE gene frequency were studied in a PCT group of patients and compared with the frequency observed in a group of ..
  35. Carroll G, Sharma G, Upadhyay A, Jazayeri J. Ferritin concentrations in synovial fluid are higher in osteoarthritis patients with HFE gene mutations (C282Y or H63D). Scand J Rheumatol. 2010;39:413-20 pubmed publisher
    ..Accordingly, it was predicted that the concentration of ferritin in synovial fluid (SF) would be higher in OA patients with HFE gene mutations than in HFE wild-type (wt) OA patients. The aim of this study was to test this proposition.
  36. Mitchell R, Freeman W, Randazzo W, Stephens H, Beard J, Simmons Z, et al. A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis. Neurology. 2009;72:14-9 pubmed publisher
    ..from neurologic disease controls, and correlates with ALS disease characteristics, and to determine the effect of HFE gene variants, a potential risk factor for sporadic ALS, on the biomarker profile...
  37. Jahanshad N, Kohannim O, Hibar D, Stein J, McMahon K, de Zubicaray G, et al. Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene. Proc Natl Acad Sci U S A. 2012;109:E851-9 pubmed publisher
    ..We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated ..
  38. Carroll G. Primary osteoarthritis in the ankle joint is associated with finger metacarpophalangeal osteoarthritis and the H63D mutation in the HFE gene: evidence for a hemochromatosis-like polyarticular osteoarthritis phenotype. J Clin Rheumatol. 2006;12:109-13 pubmed
    ..Might these conditions have common genetic characteristics? The aim of this study was to test the hypothesis that HFE gene mutations are associated with primary osteoarthritis in the ankle joint...
  39. Pedersen P, Melsen G, Milman N. Frequencies of the haemochromatosis gene (HFE) variants C282Y, H63D and S65C in 6,020 ethnic Danish men. Ann Hematol. 2008;87:735-40 pubmed publisher
    The objective was to assess the frequencies of haemochromatosis (HFE) gene mutations or variants C282Y, H63D and S65C in ethnic Danes. This is a prospective epidemiologic population study...
  40. Gunel Ozcan A, Basar M, Kisa U, Ankarali H. Hereditary haemochromatosis gene (HFE) H63D mutation shows an association with abnormal sperm motility. Mol Biol Rep. 2009;36:1709-14 pubmed publisher
    The aim of this study was to screen infertile men for HFE H63D mutation in correlation with clinical characteristics of infertile men (sperm concentration, sperm motility, morphology, testicular volume, Follicle Stimulating Hormone (FSH),..
  41. Pedersen P, Milman N. Genetic screening for HFE hemochromatosis in 6,020 Danish men: penetrance of C282Y, H63D, and S65C variants. Ann Hematol. 2009;88:775-84 pubmed publisher
    The aim of this epidemiologic population survey was to assess the penetrance of the most frequent hemochromatosis (HFE) gene variants in ethnic Danish men...
  42. Terzić R, Sehić A, Teran N, Terzic I, Peterlin B. Frequency of HFE gene mutations C282Y and H63D in Bosnia and Herzegovina. Coll Antropol. 2006;30:555-7 pubmed
    ..prevalence of the C282Y mutation in individuals of the North Western European origin, whereas lower prevalence of HFE gene mutations was detected in the populations from southern European countries...
  43. Pichler I, Minelli C, Sanna S, Tanaka T, Schwienbacher C, Naitza S, et al. Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels. Hum Mol Genet. 2011;20:1232-40 pubmed publisher
    ..In addition, we identified and replicated an association between the HFE locus and ferritin and confirmed previously reported associations with the TF, TMPRSS6 and HFE genes...
  44. Gao J, Zhao N, Knutson M, Enns C. The hereditary hemochromatosis protein, HFE, inhibits iron uptake via down-regulation of Zip14 in HepG2 cells. J Biol Chem. 2008;283:21462-8 pubmed publisher
    Lack of functional hereditary hemochromatosis protein, HFE, causes iron overload predominantly in hepatocytes, the major site of HFE expression in the liver...
  45. Benyamin B, Ferreira M, Willemsen G, Gordon S, Middelberg R, McEvoy B, et al. Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nat Genet. 2009;41:1173-5 pubmed publisher
    ..1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis. ..
  46. Mendes A, Ferro A, Martins R, Picanço I, Gomes S, Cerqueira R, et al. Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes. Ann Hematol. 2009;88:229-34 pubmed publisher
    The most frequent genotype associated with Hereditary hemochromatosis is the homozygosity for C282Y, a common HFE mutation...
  47. Carroll G, Breidahl W, Bulsara M, Olynyk J. Hereditary hemochromatosis is characterized by a clinically definable arthropathy that correlates with iron load. Arthritis Rheum. 2011;63:286-94 pubmed publisher
    ..in 10 of 41 patients with definite or probable HH (24%), all of whom were homozygous for the C282Y mutation in the HFE gene, while only 2 of 62 patients with possible/unlikely HH had such an arthropathy (P=0.0024)...
  48. Milward E, Baines S, Knuiman M, Bartholomew H, Divitini M, Ravine D, et al. Noncitrus fruits as novel dietary environmental modifiers of iron stores in people with or without HFE gene mutations. Mayo Clin Proc. 2008;83:543-9 pubmed publisher
    ..other dietary factors act as environmental modifiers of iron status in the absence or presence of hemochromatotic HFE gene mutations...
  49. Ghaziani T, Alavian S, Zali M, Shahraz S, Agah M, Jensen K, et al. Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection. Hepatol Res. 2007;37:172-8 pubmed
    We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection...
  50. Goswami T, Andrews N. Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem. 2006;281:28494-8 pubmed
    b>HFE and transferrin receptor 2 (TFR2) are membrane proteins integral to mammalian iron homeostasis and associated with human hereditary hemochromatosis...
  51. Sharifi F, Esmaeilzadeh A, Zali M. Hemochromatosis gene (HFE) mutations in patients with type 2 diabetes and their control group in an Iranian population. Saudi Med J. 2008;29:808-12 pubmed
    To assess the frequency of 2 different forms of hemochromatosis HFE gene mutations (C282Y and H63D mutations) in a normal population in comparison with type 2 diabetic patients...
  52. Bittencourt P, Marin M, Couto C, Cancado E, Carrilho F, Goldberg A. Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis. Clinics (Sao Paulo). 2009;64:837-41 pubmed publisher
    ..Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (..
  53. Martins R, Silva B, Proença D, Faustino P. Differential HFE gene expression is regulated by alternative splicing in human tissues. PLoS ONE. 2011;6:e17542 pubmed publisher
    The pathophysiology of HFE-derived Hereditary Hemochromatosis and the function of HFE protein in iron homeostasis remain uncertain...
  54. Schiepers O, van Boxtel M, de Groot R, Jolles J, de Kort W, Swinkels D, et al. Serum iron parameters, HFE C282Y genotype, and cognitive performance in older adults: results from the FACIT study. J Gerontol A Biol Sci Med Sci. 2010;65:1312-21 pubmed publisher
    ..In the present study, serum iron parameters and hemochromatosis (HFE) C282Y genotype were determined in 818 older individuals who participated in a 3-year randomized, placebo-..
  55. Sutedja N, Sinke R, Van Vught P, van der Linden M, Wokke J, van Duijn C, et al. The association between H63D mutations in HFE and amyotrophic lateral sclerosis in a Dutch population. Arch Neurol. 2007;64:63-7 pubmed
    Mutations in HFE, a gene defect that can disrupt iron metabolism, have been implicated in increasing the risk of developing amyotrophic lateral sclerosis (ALS)...
  56. Frank J, Poblete Gutierrez P, Weiskirchen R, Gressner O, Merk H, Lammert F. Hemochromatosis gene sequence deviations in German patients with porphyria cutanea tarda. Physiol Res. 2006;55 Suppl 2:S75-83 pubmed
    ..Inherited factors that may predispose to clinically overt PCT also include sequence deviations in the HFE gene that is mutated in classical hemochromatosis...
  57. Zhang A, Park S, Wright R, Weisskopf M, Mukherjee B, Nie H, et al. HFE H63D polymorphism as a modifier of the effect of cumulative lead exposure on pulse pressure: the Normative Aging Study. Environ Health Perspect. 2010;118:1261-6 pubmed publisher
    ..Polymorphisms in the hemochromatosis gene (HFE) have been shown to modify the impact of cumulative lead exposure on measures of adult cognition and cardiac ..
  58. Lawless M, White M, Mankan A, O Dwyer M, Norris S. Elevated MCP-1 serum levels are associated with the H63D mutation and not the C282Y mutation in hereditary hemochromatosis. Tissue Antigens. 2007;70:294-300 pubmed
    ..The aim of this study was to assess MCP-1 levels in patients with HH and correlate these results with HFE status and iron indexes...
  59. van der A D, Rovers M, Grobbee D, Marx J, Waalen J, Ellervik C, et al. Mutations in the HFE gene and cardiovascular disease risk: an individual patient data meta-analysis of 53 880 subjects. Circ Cardiovasc Genet. 2008;1:43-50 pubmed publisher
    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...
  60. Yu X, Wang B, Xin Z, Liu T, Ma K, Jiang J, et al. An association study of HFE gene mutation with idiopathic male infertility in the Chinese Han population. Asian J Androl. 2012;14:599-603 pubmed publisher
    Mutations in the haemochromatosis gene (HFE) influence iron status in the general population of Northern Europe, and excess iron is associated with the impairment of spermatogenesis...
  61. He X, Lu X, Hu J, Xi J, Zhou D, Shang H, et al. H63D polymorphism in the hemochromatosis gene is associated with sporadic amyotrophic lateral sclerosis in China. Eur J Neurol. 2011;18:359-61 pubmed publisher
    The H63D polymorphism in the hemochromatosis (HFE) gene has been reported as a risk factor for amyotrophic lateral sclerosis (ALS) in Europe and America, but no data have been reported for Asia...
  62. Chambers J, Zhang W, Li Y, Sehmi J, Wass M, Zabaneh D, et al. Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels. Nat Genet. 2009;41:1170-2 pubmed publisher
    ..13 (95% CI 0.09-0.17) g/dl lower per copy of allele A (P = 1.6 x 10(-13)). Our findings suggest that TMPRSS6, a regulator of hepcidin synthesis and iron handling, is crucial in hemoglobin level maintenance. ..
  63. Lin A, Yan W, Xu H, Zhu M, Zhou M. Analysis of the HFE gene (C282Y, H63D and S65C) mutations in a general Chinese Han population. Tissue Antigens. 2007;70:252-5 pubmed
    ..C282Y, H63D, and S65C are three major missense mutations of the hemochromatosis gene (HFE)...
  64. Ropero P, Briceño O, López Alonso G, Agúndez J, González Fernández F, Garcia Hoz F, et al. [The H63D mutation in the HFE gene is related to the risk of hepatocellular carcinoma]. Rev Esp Enferm Dig. 2007;99:376-81 pubmed
    To disclose whether mutations in the HFE gene inducing liver iron overload are related to the risk of hepatocellular carcinoma (HCC) in otherwise predisposed patients...
  65. Aranda N, Viteri F, Fernandez Ballart J, Murphy M, Arija V. Frequency of the hemochromatosis gene (HFE) 282C-->Y, 63H-->D, and 65S-->C mutations in a general Mediterranean population from Tarragona, Spain. Ann Hematol. 2007;86:17-21 pubmed
    Three mutations have recently been detected in the hereditary hemochromatosis HFE gene (282C-->Y, 63H-->D, and 65S-->C)...
  66. Ellervik C, Birgens H, Tybjaerg Hansen A, Nordestgaard B. Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls. Hepatology. 2007;46:1071-80 pubmed
    ..These results, mainly from case-control studies, cannot necessarily be extrapolated to the general population. ..
  67. Ezzikouri S, El Feydi A, El Kihal L, Afifi R, Benazzouz M, Hassar M, et al. Prevalence of common HFE and SERPINA1 mutations in patients with hepatocellular carcinoma in a Moroccan population. Arch Med Res. 2008;39:236-41 pubmed publisher
    ..Our objective was to estimate the prevalence of HFE and SERPINA1 (formerly known as alpha1-antitrypsin, AAT) mutations and assess their influence on hepatocellular ..
  68. de Diego C, Opazo S, Murga M, Martínez Castro P. H63D homozygotes with hyperferritinaemia: Is this genotype, the primary cause of iron overload?. Eur J Haematol. 2007;78:66-71 pubmed
    ..The simultaneous detection of 18 known HFE, TFR2 and FPN1 mutations and sequencing of the HAMP gene were performed to rule out the possible existence of ..
  69. Ali Rahmani F, Hengst J, Connor J, Schengrund C. Effect of HFE variants on sphingolipid expression by SH-SY5Y human neuroblastoma cells. Neurochem Res. 2011;36:1687-96 pubmed publisher
    C282Y and H63D are two common variants of the hemochromatosis protein HFE. SH-SY5Y human neuroblastoma cells stably transfected to express either wild type HFE (WT-HFE), or the C282Y or H63D allele were analyzed for effect of expression ..
  70. Lawless M, Mankan A, White M, O Dwyer M, Norris S. Expression of hereditary hemochromatosis C282Y HFE protein in HEK293 cells activates specific endoplasmic reticulum stress responses. BMC Cell Biol. 2007;8:30 pubmed
    ..HH) is a genetic disease associated with iron overload, in which individuals homozygous for the mutant C282Y HFE associated allele are at risk for the development of a range of disorders particularly liver disease...
  71. Santos P, Cancado R, Pereira A, Schettert I, Soares R, Pagliusi R, et al. Hereditary hemochromatosis: mutations in genes involved in iron homeostasis in Brazilian patients. Blood Cells Mol Dis. 2011;46:302-7 pubmed publisher
    p.C282Y mutation and rare variants in the HFE gene have been associated with hereditary hemochromatosis (HH)...
  72. Gurrin L, Osborne N, Constantine C, McLaren C, English D, Gertig D, et al. The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis. Gastroenterology. 2008;135:1945-52 pubmed publisher
    ..TS >95% at mean age 55 years in males increases the likelihood that SF levels will be elevated at mean age 65 years, but this effect is absent in females, most likely because of physiologic blood loss associated with menstruation. ..
  73. Hopkins M, Ettinger A, Hernandez Avila M, Schwartz J, Tellez Rojo M, Lamadrid Figueroa H, et al. Variants in iron metabolism genes predict higher blood lead levels in young children. Environ Health Perspect. 2008;116:1261-6 pubmed publisher
    ..We examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children...
  74. Lee S, Kim J, Shin S, Kang K, Choi H, Choi S, et al. HFE gene mutations, serum ferritin level, transferrin saturation, and their clinical correlates in a Korean population. Dig Dis Sci. 2009;54:879-86 pubmed publisher
    The aim of this study was to investigate HFE gene mutations, blood iron indices, and their clinical correlates in a Korean population...
  75. Soranzo N, Sanna S, Wheeler E, Gieger C, Radke D, Dupuis J, et al. Common variants at 10 genomic loci influence hemoglobin A?(C) levels via glycemic and nonglycemic pathways. Diabetes. 2010;59:3229-39 pubmed publisher
    ..6 × 10?²?), hfe (rs1800562/p = 2.6 × 10?²?), tmprss6 (rs855791/p = 2.7 × 10?¹?), ank1 (rs4737009/p = 6...
  76. Acton R, Barton J, Snively B, McLaren C, Adams P, Harris E, et al. Geographic and racial/ethnic differences in HFE mutation frequencies in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Ethn Dis. 2006;16:815-21 pubmed
    To assess geographic differences in the frequencies of HFE C282Y and H63D genotypes in six racial/ethnic groups recruited in the Hemochromatosis and Iron Overload Screening (HEIRS) Study...
  77. Allen K, Gurrin L, Constantine C, Osborne N, Delatycki M, Nicoll A, et al. Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med. 2008;358:221-30 pubmed publisher
    Most persons who are homozygous for C282Y, the HFE allele most commonly asssociated with hereditary hemochromatosis, have elevated levels of serum ferritin and transferrin saturation...
  78. Nahon P, Sutton A, Rufat P, Ziol M, Thabut G, Schischmanoff P, et al. Liver iron, HFE gene mutations, and hepatocellular carcinoma occurrence in patients with cirrhosis. Gastroenterology. 2008;134:102-10 pubmed
    The influence of HFE gene mutations and liver iron overload on hepatocellular carcinoma (HCC) occurrence in patients with cirrhosis is subjected to controversial results...
  79. Lee S, Liu S, Mitchell R, Slagle Webb B, Hong Y, Sheehan J, et al. HFE polymorphisms influence the response to chemotherapeutic agents via induction of p16INK4A. Int J Cancer. 2011;129:2104-14 pubmed publisher
    b>HFE is a protein that impacts cellular iron uptake. HFE gene variants are identified as risk factors or modifiers for multiple diseases...