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Comparative Study of the Two More Frequent HFE Mutations
(C282Y and H63D): Significant Different Allelic Frequencies Between the North and South of Portugal

May 23, 2001

Reviewed by:

Lisa Kalman
National Center for Environmental Health
Centers for Disease Control and Prevention

The Health Outcome

One of the most common autosomal recessive disorders in Caucasians is hereditary hemochromatosis. Worldwide, the allele frequency is approximately two percent for the C282Y mutation and eight percent for the H63D mutation. The C282Y mutation is most prevalent in Northern European populations and absent from African, Asian, and Australasian populations (1). The H63D mutation is found in almost all populations studied, with the highest frequency (30%) among the Basque population (1). In Caucasian populations, about one person in 300 are affected with the disease (2,3). Mutations of the HFE gene cause increased iron absorption leading to excess iron in the parenchymal cells in several organs. This can lead to health affects such as cirrhosis of the liver, hepatocellular carcinoma, diabetes, heart failure, arthritis, and hypogonadism. Early detection and treatment can prevent morbidity and mortality from this disease .


The Finding

This population-based study reports the geographic distribution of two alleles of the HFE gene. Data on allelic distribution were derived from randomly selected dried blood spots collected for newborn metabolic screening.  In Portugal , the allelic frequency of the more common C282Y mutation was higher in the north (0.058) than in the south (0.009).  The allelic frequency of the H63D did not differ by regions of the country (4).


Public Health Implications

The geographical distribution of the two main HFE alleles was not uniform.  The authors postulate that the C282Y mutation may confer a selective advantage in the northern regions of Portugal.  Heterozygotes may be protected from iron deficiency from diet and blood loss.  This mutation, which causes higher iron retention, may be a selective disadvantage in the southern regions, where the incidence of malaria is high.  Other studies have found that C282Y is more common in northern Europe and less common in southern Europe.  This information may be useful in targeting populations for screening.  These results are based on small numbers, and additional research is needed.  Additionally, more data on prevalence of different genotypes are needed before these data can be properly interpreted.

References

  1. Merryweather-Clarke, A.R., Pointon, J.J.,Shearman, J.D., Robson, K.J. (1997) Global prevalence of putative haemochromatosis mutations. J. Med. Genet. 34:275-78.
  2. Cullen, L.M., Anderson , G.J., Ramm, G.A., Jazwinska, E.C., and Powell, L.W.  (1999).  Genetics of hemachromatosis.  Annu. Rev. Med. 50:87-98.
  3. Edwards, C.Q., Griffen, L.M., Goldgar, D.E., Drummond, C., Skolnick, M.H., Kushner, J.P. (1988) Prevalence of hemochromatosis among 11,065 presumably healthy blood donors.  N. Engl. J. Med.  318:1355-1362.
  4. Cardoso C, Oliveira P, Porto G, Oberkanins C, Mascarenhas M, Rodrigues P, Kury F, de Sousa M.  Comparative study of the two more frequent HFE mutations (C282Y and H63D): significant different allelic frequencies between the North and South of Portugal.  Eur Hum Gene. 2001 9:843- 8.
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Last Updated August 18, 2004