International Journal of Hematology

, Volume 77, Issue 1, pp 48–54

Frequencies of the Hereditary Hemochromatosis Allele in Different Populations. Comparison of Previous Phenotypic Methods and Novel Genotypic Methods

  • Nils Milman
  • Palle Pedersen
  • Torkil á Steig
  • Gitte Vedel Melsen

DOI: 10.1007/BF02982602

Cite this article as:
Milman, N., Pedersen, P., á Steig, T. et al. Int J Hematol (2003) 77: 48. doi:10.1007/BF02982602



The frequencies of the hereditary hemochromatosis allele were compared for different populations assessed by previous phenotypic methods and the present genotypic methods.


From a literature survey, the calculated hemochromatosis allele frequencies from 16 studies using phenotypic biochemical markers (threshold levels for transferrin saturation [range, 46%–70%] and serum ferritin [range, 164–700 µg/L]) were compared with allele frequencies of the Cys282Tyr mutation of the hemochromatosis gene reported in 19 genotypic studies.


Calculated phenotypic allele frequencies are high in Scandinavia: Iceland, 6.1% to 7.4%; Norway, 5.8%; central Sweden, 6.3% to 6.9%; Denmark, 6.1%. Frequencies are similarly high in Wales, Canada, Utah, South Africa, and Australia (range, 5.2%–9.8%). Frequencies are low in Finland (1.9%) and northern Italy (4.5%). Genotypic allele frequencies of the Cys282Tyr mutation are likewise high in Scandinavia. Frequencies are high in the United Kingdom and northern France and low in Finland, central Germany, northern Italy, and Greece. The phenotypic-genotypic ratios of the hemochromatosis homozygosity frequencies for the same geographic area were calculated. A ratio of 1.0 indicates that the 2 methods give similar results. In 3 studies, the ratio was above 1.0, the highest ratio of 1.67 being reported from Italy. In most studies the ratio was slightly below 1.0 (0.71–0.97). The lowest ratio was found in Finland (0.33).


In most studies there was good agreement between the hemochromatosis allele frequencies determined by phenotypic and genotypic methods. A high ratio (northern Italy) may indicate that phenotypic selection criteria were too loose and/or that causes of iron overload other than the Cys282Tyr mutation are frequent in the region. A low ratio (in Finland) may indicate phenotypic selection criteria that were too stringent and/or a low penetration rate of the mutation.

Key words

Denmark Hemochromatosis Prevalence Scandinavia 

Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  • Nils Milman
    • 1
  • Palle Pedersen
    • 2
  • Torkil á Steig
    • 3
  • Gitte Vedel Melsen
    • 2
  1. 1.Department of Medicine B, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Clinical BiochemistryNæstved HospitalNæstvedDenmark
  3. 3.Department of Medicine and the Blood BankLandssukrahusidTórshavnFaeroe Islands