Skip to main content
SpringerLink
Log in

Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal)

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

Abstract

Hereditary HFE Hemochromatosis is an inherited disorder of iron metabolism that results from mutations in the HFE gene. Almost all patients with hereditary hemochromatosis show a C282Y mutation in homozygosity or in compound heterozygosity with H63D. Also, the mutation S65C has been shown to be associated to a milder iron overload. Since allele and genotype frequencies of these three variants of the HFE gene vary between populations, the determination of their prevalence in Madeira Island will clarify the population susceptibility to hereditary hemochromatosis. One hundred and fifty-four samples from Madeira Island were genotyped for the three most common HFE gene mutations, H63D, C282Y, and S65C, by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results have shown a prevalence of 20.5%, 0.33%, and 1% for H63D, C282Y, and S65C, respectively. Accordingly to our estimates, both genotypes associated to hereditary hemochromatosis, C282Y homozygotes and C282/H63D compound heterozygotes, could be present in Madeira Island population in 1,648 individuals, which represents 0.65% of the total population.

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. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408

    Article  CAS  PubMed  Google Scholar 

  2. Altes A, Ruiz A, Martinez C, Esteve A, Vela MD, Remacha AF et al (2007) The relationship between iron overload and clinical characteristics in a Spanish cohort of 100 C282Y homozygous hemochromatosis patients. Ann Hematol 86:831–835

    Article  PubMed  Google Scholar 

  3. Aranda N, Viteri FE, Montserrat C, Arija V (2010) 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 (Germany) 89:767–773

    CAS  Google Scholar 

  4. Fairbanks VF, Klee GG (1999) Biochemical aspects of hematology. In: Burtis CA, Ashwood ER (eds) Tietz textbook of clinical chemistry, 3rd edn. Saunders, Philadelphia, pp 1642–1710

    Google Scholar 

  5. Pedersen P, Milman N (2009) Genetic screening for HFE hemochromatosis in 6, 020 Danish men: penetrance of C282Y, H63D, and S65C variants. Ann Hematol (Germany) 88:775–784

    CAS  Google Scholar 

  6. Simon M, Bourel M, Fauchet R, Genetet B (1976) Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut 17:332–334

    Article  CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  8. Tavill AS (2001) Diagnosis and management of hemochromatosis. Hepatology 33:1321–1328. doi:10.1053/jhep.2001.24783

    Article  CAS  PubMed  Google Scholar 

  9. Douabin V, Deugnier Y, Jouanolle AM, Moirand R, Macqueron G, Gireau A, Le Gall JY, David V (1997) Polymorphisms in the haemochromatosis gene. International Symposium on Iron in Biology and Medicine. Saint-Malo, France, p 267

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  11. Mendes AI, Ferro A, Martins R, Picanço I, Gomes S, Cerqueira R et al (2009) Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes. Ann Hematol (Germany) 88:229–234

    CAS  Google Scholar 

  12. Cimburová M, Putová I, Provazníková H, Pintérová D, Horák J (2005) S65C and other mutations in the haemochromatosis gene in the Czech population. Folia Biologica (Praha) 51:172–176

    Google Scholar 

  13. 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  CAS  PubMed  Google Scholar 

  14. Pedersen P, Melsen GV, Milman N (2008) Frequencies of the haemochromatosis gene (HFE) variants C282Y, H63D and S65C in 6,020 ethnic Danish men. Ann Hematol (Germany) 87:735–740

    Google Scholar 

  15. Porto G, Alves H, Rodrigues P, Cabeda JM, Portal C, Ruivo A, Justica B, Wolff R, De Sousa M (1998) 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. Immunogenetics 47:404–410

    Article  CAS  PubMed  Google Scholar 

  16. Carreira A (1983) Migrações nas Ilhas de Cabo Verde, 2nd edn. Instituto Cabo verdeano do Livro, Lisboa

    Google Scholar 

  17. Russel-Wood AJ (1998) The Portuguese empire. 1415–1808. A world on the move. The Johns Hopkins University Press, Baltimore

    Google Scholar 

  18. Fernandes AT, Brehm A, Gusmão L, Amorim A (2001) Y-chromosome STR haplotypes in the Madeira archipelago population. Forensic Sci Int 122:178–180

    Article  CAS  PubMed  Google Scholar 

  19. Brehm A, Pereira L, Kivisild T, Amorim A (2003) Mithocondrial portraits of the Madeira and Açores archipelagos witness different genetic pools of its settlers. Hum Genet 114:77–86

    Article  CAS  PubMed  Google Scholar 

  20. Spínola H, Brehm A, Williams F, Jesus J, Middleton D (2002) Distribution of HLA alleles in Portugal and Cabo Verde. Relationships with the slave trade route. Ann Hum Genet 66:285–296

    Article  PubMed  Google Scholar 

  21. Spínola H, Bruges-Armas J, Mora MG, Middleton D, Brehm A (2006) HLA genes in Madeira Island (Portugal) inferred from sequence-based typing: Footprints from different origins. Mol Immunol 43:1726–1728

    Article  PubMed  Google Scholar 

  22. 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

    Article  CAS  PubMed  Google Scholar 

  23. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Wolfe R, Cumming G (2004) Communicating the uncertainty in research findings: confidence intervals. J Sci Med Sport 7:138–143

    Article  CAS  PubMed  Google Scholar 

  26. Agresti A (1992) A survey of exact inference for contingency tables. Stat Sci 7:131–153

    Article  Google Scholar 

  27. Excoffier LG, Laval G, Schneider S (2005) Arlequin version 3.0: an integrated software package for population genetics data analysis. Evol Bioinformatics Online 1:47–50

    CAS  Google Scholar 

  28. Couto AR, Peixoto MJ, Garret F, Laranjeira F, Cipriano T, Bruges-Armas J (2003) Linkage disequilibrium between S65C HFE mutation and HLA A29-B44 Haplotype in Terceira Island, Azores. Hum Immunol 64:625–628

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by Intervir+ program from Madeira Autonomous Region (Portugal) and European Community, as well as BIOFORMA and SANTOQUEIJO.

Author information

Authors and Affiliations

  1. Human Genetics Laboratory, University of Madeira, Campus da Penteada, 9000-390, Funchal, Portugal

    Carla Spínola, António Brehm & Hélder Spínola

Authors
  1. Carla Spínola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. António Brehm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hélder Spínola
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hélder Spínola.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spínola, C., Brehm, A. & Spínola, H. Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal). Ann Hematol 90, 29–32 (2011). https://doi.org/10.1007/s00277-010-1034-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-010-1034-x

Keywords

Search

Navigation