Longevity and C282Y mutation for haemochromatosis: Survival of C282Y homozygotes does not preclude screening for HFE mutations

BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7421.990-a (Published 23 October 2003) Cite this as: BMJ 2003;327:990
  1. Gavin Willis, clinical scientist (gavin.willis{at}nnuh.nhs.uk),
  2. Barbara A Jennings, lecturer in molecular medicine,
  3. Jennie Z Wimperis, consultant haematologist
  1. Molecular Genetics, Norfolk and Norwich University Hospital, Norwich NR4 7UY
  2. School of Medicine, University of East Anglia, Norwich NR4 7TJ
  3. Department of Haematology, Norfolk and Norwich University Hospital

    EDITOR–In their recent paper, Coppin et al found surviving elderly people who were homozygous for the C282Y mutation at a frequency similar to our previous study.1 2 Their results illustrate clearly and simply that fatal disease is not an invariant outcome for untreated women who are homozygous for the C282Y mutation, and our study drew the same conclusion for homozygous men.

    Coppin et al say that their results preclude the use of HFE C282Y testing for screening. This is an overinterpretation of the data for two reasons.

    Firstly, the power of this study to determine the proportion of people who are homozygous for the C282Y mutation who die prematurely (penetrance) is low: the 95% confidence interval for the observed two people is 0.24 to 7.19. The 95% confidence interval for penetrance is therefore somewhere between 0% and 80%.

    Secondly, their assertion ignores the fact that C282Y homozygosity is clearly linked to life threatening disease. HFE testing may be a better first line screening test than iron indices because it is independent of iron intake and loss. It can therefore identify individuals who may subsequently develop iron overload–for, example menstruating women. Targeted HFE testing can identify people who are homozygous for the C282Y mutation at a lower cost per life saved than other currently accepted screening tests even if penetrance is below 10%3: it is the subsequent cost of lifelong treatment that makes the overall cost of population screening unfavourable.

    The current problem is that iron indices do not reliably distinguish which people with the C282Y mutation will develop disease. Accepted practice is that no one with an iron overload can be left untreated. What is required is a further test that would allow the selective treatment of the subset at risk.


    • Competing interests None declared.


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