Abstract
C282Y/C282Y genotype is the prevalent genotype in Hereditary Haemochromatosis (HH), however, other genotypes have been associated with the disease. The objective of our study was to analyse the frequency of the three main mutations of HFE gene in HH patients and controls from the Basque population with differential genetic characteristics. Thirty five HH patients and 116 controls were screened for C282Y, H63D and S65C mutations using a PCR–RFLP technique. The association of HLA-A and-B alleles and HFE mutations was also studied in Basque controls. The frequency of C282Y homozygotes in the group of patients was only 57%. The rest of the patients presented heterogeneous genotypes, including compound heterozygotes: 11% of them were C282Y/H63D; and 2.85% were H63D/S65C. H63D or S65C heterozygotes had a frequency of 11% and 2.85 respectively and 5.71% patients lacked any mutation The high frequency of H63D in the healthy Basque population is confirmed in this study. A considerable incidence of S65C is observed either in controls and in HH (3%) or in iron overloaded patients. The peculiar genetic characteristics of Basques could explain the heterogeneity of genotypes in HH patients of this group. Further studies should be carried out to confirm these findings although the implication of other genetic or external factors in the development of HH is suggested.
Similar content being viewed by others
Article PDF
References
Simon M, Bourel M, Fauchet R, Genetet B . Association of HLA-A3 and B14 antigens with idiopathic hemochromatosis Gut 1976 17: 332–334
Feder JN, Gnirke A, Thomas W et al. A novel MHC class I-like is mutated in patients with hereditary haemochromatosis Nature Genet 1996 13: 399–408
Lebrón JA, Bennett MJ, Vaughn DE et al. Crystal structure of the hemochromatosis protein HFE and characterisation of its interaction with transferrin receptor Cell 1998 93: 111–123
Merryweather-Clarke AT, Pointon JJ, Jouanolle AM, Rochette J, Robson KJH . Geography of HFE C282Y and H63D mutations Genet Testing 2000 4: 183–198
Mura C, Raguenes O, Férec C . HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis Blood 1999 93: 2502–2505
Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJH . Global prevalence of putative haemochromatosis mutations J Med Genet 1997 34: 275–278
Calafell F, Bertranpetit J . Principal component analysis in gene frequencies and the origin of the Basques Am J Phys Anthropol 1994 93: 201–215
Cavalli-Sforza LL . The Basque population ancient migrations in Europe Munibe 1988 6: suppl 129–137
Martinez-Laso J, De Juan MD, Martinez Quiles N, Gomez Casado E, Cuadrado E, Arnaiz-Villena A . The contribution of the HLA-A, -B, -C and DR, -DQ DNA typing to the study of the origins of Spaniards and Basques Tissue Antigens 1995 45: 237–245
Adams P, Brissot P, Powell LW . EASL International Consensus Conference on Hemochromatosis. Expert Document J Hepatol 2000 33: 485–504
Powell LW, George DK, Mc Donell SM, Kowdley KV . Diagnosis of hemochromatosis Ann Intern Med 1998 129: 925–931
Svejaard A, Ryder LP . HLA and disease associations: Detecting the strongest association Tissue Antigens 1994 43: 18–27
Sanchez M, Brugera M, Bosch J, Rodés J, Ballesta F, Oliva R . Prevalence of the Cys282Tyr and His63Asp HFE gene mutations in Spanish patients with hereditary hemochromatosis and in controls J Hepatol 1998 29: 725–728
Pardo A . Hemocromatosis Hereditaria (HH) en España. Impacto del diagnóstico genético Gastroenterologia y Hepatologia 2001 24: 112
Rochette J, Pointon JJ, Fisher CA et al. Multicentric origin of hemachromatosis gene (HFE) mutations Am J Hum Genet 1999 64: 1056–1062
Barton JC, Sawada-Hirai R, Rothenberg BE, Acton R . Two novel missense mutations of the HFE gene (I105C and G93R) and identification of the S65C mutation in Alabama hemochromatosis probands Blood Cells Mol Dis 1999 25: 147–155
Casals T, Vazquez C, Lazaro C, Girbau E, Gimenez FJ, Estivill X . Cystic Fibrosis in the Basque country: High frequency of mutation ΔF508 in patients of Basque origin Am J Hum Genet 1992 50: 404–410
Piperno A, Sampietro M, Pietrangelo A et al. Heterogeneity of hemochromatosis in Italy Gastroenterology 1998 114: 996–1002
Mercier G, Burckel A, Bathelier C, Boillat E, Lucotte G . Mutation analysis of the HLA-H gene in French hemochromatosis patients and genetic counseling in families Genet Couns 1998 9: 181–186
Rosmorduc O, Poupon R, Nion I et al. Differential HFE allele expression in hemochromatosis heterozygotes Gastroenterology 2000 119: 1075–1086
Aguilar-Martinez P, Thelcide C, Jeanjean P, Masmejean C, Giansily M, Schved JF . Haplotype analysis of the HFE gene: Implications for the origins of hemochromatosis related mutations Blood Cells, Molecules, and Diseases 1999 15: 166–169
Porto G, Alves H, Rodrigues P et al. 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 1998 47: 404–410
Njajou OT, Vaessen N, Joosse M, Berghuis B, Van Dongen JWF, Breuning M H, et al. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis Nature Genet 2001 28: 213–214
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
de Juan, M., Reta, A., Castiella, A. et al. HFE gene mutations analysis in Basque hereditary haemochromatosis patients and controls. Eur J Hum Genet 9, 961–964 (2001). https://doi.org/10.1038/sj.ejhg.5200731
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ejhg.5200731
Keywords
This article is cited by
-
EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)
European Journal of Human Genetics (2016)
-
Gender and plasma iron biomarkers, but not HFE gene mutations, increase the risk of colorectal cancer and polyps
Tumor Biology (2015)
-
Prevalence of C282Y, H63D, and S65C mutations in hereditary HFE-hemochromatosis gene in Lithuanian population
Annals of Hematology (2012)
-
Prevalence of H63D, S65C and C282Y hereditary hemochromatosis gene mutations in Slovenian population by an improved high-throughput genotyping assay
BMC Medical Genetics (2007)
-
Genetic relationship between Murcia Region (SE Spain) and other populations in the Iberian Peninsula and Mediterranean area with respect to HFE gene mutations distribution
Annals of Hematology (2007)