Skip to main content
SpringerLink
Log in

Frequency of the hemochromatosis gene (HFE) 282C→Y, 63H→D, and 65S→C mutations in a general Mediterranean population from Tarragona, Spain

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Three mutations have recently been detected in the hereditary hemochromatosis HFE gene (282C→Y, 63H→D, and 65S→C). To determine their prevalence in a northeastern Spanish Mediterranean population, we studied 812 subjects between 18 and 75 years of age, randomly selected from the electoral roll of three villages. There were no homozygotes for the 282C→Y or S65D mutations in this sample. For the 63H→D mutation, 4.8% were homozygotes; 4.3, 32.3, and 2% were heterozygotes for the 282C→Y, 63H→D, and 65S→C mutations, respectively. The prevalence of compound heterozygotes was 2% for 282C→Y/63H→D and 0.6% for 63H→D /65S→C. We found no significant differences between men and women. In conclusion, 46% of this Mediterranean population of Spain are carriers of at least one of the three mutations that can increase iron absorption.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Adams PC, Brissot P, Powell LW (2000) EASL international consensus conference on haemochromatosis. J Hepatol 33:485–504

    Article  PubMed  CAS  Google Scholar 

  2. Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, Dawkins FW, Acton RT, Harris EL, Gordeuk VR, Leiendecker-Foster C, Speechley M, Snively, Holup JL, Thomson E, Sholinsky P (2005) Hemochromatosis and iron-overload. Screening in a racially diverse population. N Engl J Med 352:1769–1778

    Article  PubMed  CAS  Google Scholar 

  3. Alvarez S, Mesa MS, Bandres F, Arroyo E (2001) C282Y and H63D mutation frequencies in a population from central Spain. Dis Markers 17:111–114

    PubMed  CAS  Google Scholar 

  4. Barton JC, Sawada-Hirai R, Rothenberg BE, Acton RT (1999) Two novel missense mutations of the HFE gene (I105T and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands. Blood Cells Mol Dis 25:147–155

    Article  PubMed  CAS  Google Scholar 

  5. Barton JC, Rivers CA, Niyongere S, Bohannon SB, Acton RT (2004) Allele frequencies of hemojuvelin gene (HJV) I222N and G320 V missense mutations in white and African American subjects from the general Alabama population. BMC Med Genet 5:29

    Article  PubMed  CAS  Google Scholar 

  6. Bell H, Berg JP, Undlien DE, Distante S, Raknerud N, Heier HE, Try K, Thomassen Y, Haug E, Raha-Chowdhury R, Thorsby E (2000) The clinical expression of hemochromatosis in Oslo, Norway. Excessive oral iron intake may lead to secondary hemochromatosis even in HFE C282Y mutation negative subjects. Scand J Gastroenterol 35:1301–1307

    Article  PubMed  CAS  Google Scholar 

  7. Beutler E, Felitti V, Gelbart T, Ho N (2000) The effect of HFE genotypes on measurements of iron overload in patients attending a health appraisal clinic. Ann Intern Med 133:329–337

    PubMed  CAS  Google Scholar 

  8. Beutler E, Felitti VJ, Koziol JA, Ho NJ, Gelbart T (2002) Penetrance of 845G-> A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 359:211–218

    Article  PubMed  Google Scholar 

  9. Beutler E, Felitti VJ (2003) The clinical penetrance of hereditary hemochromatosis. Hepatology 37:711

    Article  PubMed  Google Scholar 

  10. Beutler E (2006) Hemochromatosis: genetics and pathophysiology. Annu Rev Med 57:5.1–5.17

    Article  CAS  Google Scholar 

  11. Bradley LA, Johnson DD, Palomaki GE, Haddow JE, Robertson NH, Ferrie RM (1998) Hereditary haemochromatosis mutation frequencies in the general population. J Med Screen 5:34–36

    PubMed  CAS  Google Scholar 

  12. Burt MJ, George PM, Upton JD, Collett JA, Frampton CM, Chapman TM, Walmsley TA, Chapman BA (1998) The significance of haemochromatosis gene mutations in the general population implications for screening. Gut 43:830–836

    Article  PubMed  CAS  Google Scholar 

  13. Campbell S, George DK, Robb SD, Spooner R, McDonagh TA, Dargie HJ, Mills PR (2003) The prevalence of haemochromatosis gene mutations in the west of Scotland and their relation to ischaemic heart disease. Heart 89:1023–1026

    Article  PubMed  CAS  Google Scholar 

  14. Cardoso CS, Oliveira P, Porto G, Oberkanins C, Mascarenhas M, Rodrigues P, Kury F, Sousa M (2001) Comparative study of the two more frequent HFE mutations (C282Y and H63D): significant different allelic frequencies between the north and south of Portugal. Eur J Hum Genet 9:843–848

    PubMed  CAS  Google Scholar 

  15. de Juan D, Reta A, Castiella A, Pozueta J, Prada A, Cuadrado E (2001) HFE gene mutations analysis in Basque hereditary haemochromatosis patients and controls. Eur J Hum Genet 9:961–964

    Article  PubMed  CAS  Google Scholar 

  16. Fábrega E, Castro B, Sánchez-Castro L, Benito A, Fernández-Luna JL, Pons-Romero F (1999) Prevalencia de la mutación Cys282Tyr del gen de la hemocromatosis en Cantabria y en los pacientes diagnosticados de hemochromatosis hereditaria. Med Clin (Barc) 112:451–453

    Google Scholar 

  17. Feder JN, Tsuchihashi Z, Irrinki A, Lee VK, Mapa FA, Morikang E, Prass CE, Starnes SM, Wolff RK, Parkkila S, Sly WS, Schatzman RC (1997) The hemochromatosis founder mutation in HLA-H disrupts beta-2-microglobulin interaction and cell surface expresion. J Biol Chem 272:14025–14028

    Article  PubMed  CAS  Google Scholar 

  18. Gordeuk VR, Caleffi A, Corradini E, Ferrara F, Jones RA, Castro O, Onyekwere O, Kittles R, Pignatti E, Montosi G, Garuti C, Gangaidzo IT, Gomo ZA, Moyo VM, Rouault TA, MacPhail P, Pietrangelo A (2003) Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene. Blood Cells Mol Dis 31:299–304

    Article  PubMed  CAS  Google Scholar 

  19. Guix P, Picornell A, Parera M, Tomas C, Muncunill J, Castro JA, Rossell J, Vaquer P, Ramon MM, Obrador A (2000) Prevalence of the C282Y mutation for haemochromatosis on the island of Majorca. Clin Genet 58:123–128

    Article  PubMed  CAS  Google Scholar 

  20. Guix P, Picornell A, Parera M, Galmes A, Obrador A, Ramon MM, Castro JA (2002) Distribution of HFE C282Y and H63D mutations in the Balearic Islands (NE Spain). Clin Genet 61:43–48

    Article  PubMed  CAS  Google Scholar 

  21. Hanson EH, Imperatore G, Burke W (2001) HFE gene and hereditary hemochromatosis: a huge review. Human genome epidemiology. Am J Epidemiol 154:193–206

    Article  PubMed  CAS  Google Scholar 

  22. Holmströn P, Marmur J, Eggertsen G, Gafvels M, Stal P (2002) Mild iron overload in patients carrying the HFE S65C gene mutation: a retrospective study in patients with suspected iron overload and healthy controls. Gut 51:723–730

    Article  Google Scholar 

  23. Jackson HA, Carter K, Darke C, Guttridge MG, Ravine D, Hutton RD, Napier JS, Worwood M (2001) HFE mutations, iron deficiency and overload in 10500 blood donors. Br J Haematol 114:474–484

    Article  PubMed  Google Scholar 

  24. Jouanolle AM, Fergelot P, Gandon G, Yaouanq J, Le Gall JY, David V (1997) A candidate gene for hemochromatosis: frequency of the C282Y and H63D mutations. Hum Genet 100:544–547

    Article  PubMed  CAS  Google Scholar 

  25. Lucotte G, Dieterlen F (2003) A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation? Blood Cells Mol Dis 31:262–267

    Article  PubMed  CAS  Google Scholar 

  26. McNamara L, MacPhail AP, Gordeuk VR, Hasstedt SJ, Rouault T (1998) Is there a link between African iron overload and the described mutations of the hereditary haemochromatosis gene? Br J Haematol 102:1176–1178

    Article  PubMed  CAS  Google Scholar 

  27. Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ (1997) Global prevalence of putative haemochromatosis mutations. J Med Genet 34:275–278

    Article  PubMed  CAS  Google Scholar 

  28. Merryweather-Clarke AT, Pointon JJ, Jouanolle AM et al (2000) Geography of the C282Y and H63D mutations. Genet Test 4:183–198

    Article  PubMed  CAS  Google Scholar 

  29. Milman N, Pedersen P (2003) Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in southern Scandinavia and spread with the Vikings. Clin Genet 64:36–47

    Article  PubMed  CAS  Google Scholar 

  30. Milman N, Pedersen P, Ovesen L, Melsen GV, Fenger K (2004) Frequency of the C282Y and H63D mutations of the hemochromatosis gene (HFE) in 2501 ethnic Danes. Ann Hematol 83:654–657

    Article  PubMed  CAS  Google Scholar 

  31. Milman N, a Steig T, Koefoed P, Pedersen P, Fenger K, Nielsen FC (2005) Frequency of the hemochromatosis HFE mutations C282Y, H63D, and S65C in blood donors in the Faroe Islands. Ann Hematol 84:146–149

    Article  PubMed  CAS  Google Scholar 

  32. Mura C, Raguenes O, Férec C (1999) HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implications in mild form of hemochomatosis. Blood 93:2502–2505

    PubMed  CAS  Google Scholar 

  33. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW (1999) A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 341:718–724

    Article  PubMed  CAS  Google Scholar 

  34. Pietrangelo A (2004) Hereditary hemochromatosis—a new look at an old disease. N Engl J Med 50:2383–2397

    Article  Google Scholar 

  35. Sánchez M, Bruguera M, Bosch J, Rodes J, Ballesta F, Oliva R (1998) Prevalence of the Cys282Tyr and His63Asp HFE gene mutations in Spanish patients with hereditary hemochromatosis and in controls. J Hepatol 29:725–728

    Article  PubMed  Google Scholar 

  36. Sánchez M, Villa M, Ingelmo M, Sanz C, Bruguera M, Ascaso C, Oliva R (2003) Population screening for hemochromatosis: a study in 5370 Spanish blood donors. J Hepatol 38:745–750

    Article  PubMed  Google Scholar 

  37. Soto L, Vega A, Goyanes V, Valverde D (2000) Hemochromatosis in Galicia (NW Spain): a Celtic influence? Clin Genet 57:454–455

    Article  PubMed  CAS  Google Scholar 

  38. Waheed A, Parkkila S, Zhou XY, Tomatsu S, Tsuchihashi Z, Feder JN, Schatzman RC, Britton RS, Bacon BR, Sly WS (1997) Hereditary hemochromatosis: Effects of C282Y and H63D mutations on association with ß2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. Proc Natl Acad Sci U S A 94:12384–12389

    Article  PubMed  CAS  Google Scholar 

  39. Waheed A, Grubb JH, Yan Zhou X, Tomatsu S, Fleming RE, Costaldi ME, Britton RS, Bacon BR, Sly WS (2002) Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis. Proc Natl Acad Sci USA 99:3117–3122

    Article  PubMed  CAS  Google Scholar 

  40. Waalen J, Felitti V, Gelbart T, Ho NJ, Beutler E (2002) Prevalence of hemochromatosis-related symptoms among individuals with mutations in the HFE gene. Mayo Clin Proc 77:522–530

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by three grants from the Instituto de Salud Carlos III, Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo, Madrid, Spain (PI021131); Red de Centros RCMN, Madrid, Spain (C03/08); and Red de Grupos, Madrid, Spain (G03/140), and by NIH National Center on Minority Health and Health Disparities grant IP60MD000222-03 (for Dr. Viteri).

Author information

Authors and Affiliations

  1. Preventive Medicine and Public Health, Faculty of Medicine and Health Sciences, Rovira i Virgili University, C/ Sant Llorenç 21, 43201, Reus, Spain

    Núria Aranda, Joan Fernández-Ballart, Michelle Murphy & Victoria Arija

  2. Nutritional Sciences and Toxicology, Morgan Hall, University of California, Children’s Hospital Oakland Research Institute (CHORI), Oakland 5700 Martin Luther King Way, Oakland, CA, 94609, USA

    Fernando E. Viteri

Authors
  1. Núria Aranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernando E. Viteri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joan Fernández-Ballart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelle Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Victoria Arija
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victoria Arija.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aranda, N., Viteri, F.E., Fernández-Ballart, J. et al. Frequency of the hemochromatosis gene (HFE) 282C→Y, 63H→D, and 65S→C mutations in a general Mediterranean population from Tarragona, Spain. Ann Hematol 86, 17–21 (2007). https://doi.org/10.1007/s00277-006-0179-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-006-0179-0

Keywords

Search

Navigation