The effect of HFE mutations on serum ferritin and transferrin saturation in the Jersey population

@article{MerryweatherClarke1998TheEO,
  title={The effect of HFE mutations on serum ferritin and transferrin saturation in the Jersey population},
  author={Alison T. Merryweather-Clarke and Mark Worwood and L. Parkinson and Christopher Mattock and Jennifer J. Pointon and Jeremy D. Shearman and Kathryn J. H. Robson},
  journal={British Journal of Haematology},
  year={1998},
  volume={101}
}
High frequencies of the haemochromatosis‐related HFE C282Y mutation have been reported in North European populations, in which a high proportion of patients with the disease are homozygotes. However, the degree of penetrance of this genotype is unknown. We determined the HFE C282Y and H63D genotypes of 411 consenting volunteer blood donors on Jersey, and the serum ferritin and transferrin saturation levels of 204 of these volunteers. The C282Y allele frequency was found to be 8.3% in 822… 
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89 Citations
Highly Influential Citations
3
Background Citations
15
Methods Citations
2
Results Citations
6

89 Citations

Frequency and clinical expression of HFE gene mutations in a Spanish population of subjects with abnormal iron metabolism
TLDR
TSI and serum ferritin values detected most HFE C282Y variant homozygotes and are recommended to facilitate the clinical diagnosis of HH and very significant differences in serum iron values were observed.
HFE mutations, iron deficiency and overload in 10 500 blood donors
TLDR
Donors lacking the mutations and donors homozygous for H63D and C282Y were at no greater risk of iron accumulation than donors lacking mutations, and serum ferritin concentrations were no higher in H 63D heterozygotes and C281Y heterozygous women than in donors lacking mutation.
HFE genotype and parameters of iron metabolism in German first-time blood donors - evidence for an increased transferrin saturation in C282Y heterozygotes.
TLDR
The elevated TS in subjects carrying a single copy of the C282y mutation suggests that C282Y heterozygosity is associated with an increased intestinal iron absorption and might therefore offer a selection advantage in conditions of iron depletion.
Correlation between iron status and genetic hemochromatosis (codon C282Y) in a large German population.
TLDR
Heterozygous individuals with higher transferrin saturation values may be protected against iron loss but may also be more susceptible for certain liver diseases, depending on the simultaneous prevalence of other diseases.
Haemochromatosis-associated HFE genotypes in English blood donors: age-related frequency and biochemical expression.
Mutation analysis of the HFE gene associated with hereditary hemochromatosis in a Venezuelan sample
TLDR
The results suggest that the admixture of native populations with subjects of South European origin might have had an important role in the diffusion of HFE alleles in Venezuela, and indicates that C282Y homozygotes will be rarely detected.
Compound heterozygous hemochromatosis genotype predicts increased iron and erythrocyte indices in women.
TLDR
It is concluded that the compound heterozygous HFE genotype C282Y/H63D, but not the C282y wild-type genotype, had increased values for serum iron and transferrin saturation, and the younger age group also had increased hemoglobin values.
Low penetrant hemochromatosis phenotype in eight families: no evidence of modifiers in the MHC region.
TLDR
These studies suggest that neither HFE polymorphism nor genes surrounding HFE are able to modulate HFE expression, suggesting incomplete penetrance of the mutation.
HFE Mutations as risk factors in disease.
  • M. Worwood
  • Biology, Medicine
    Best practice & research. Clinical haematology
  • 2002
TLDR
Testing for HFE mutations in clinics for diabetes, liver disease and cardiovascular disease has shown that homozygosity for C282Y is not commonly found and does not appear to be a risk factor for these common conditions.
Polymorphism of the HFE Gene Associated with Hereditary Hemochromatosis in Populations of Russia
TLDR
The HFE allele frequency distribution patterns observed in the populations examined pointed to pre-Celtic appearance of the C282Y allele, which provides an explanation of the evolutionary genetic relationships between Siberian ethnic groups and the contemporary populations of Eastern and Western Europe.
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References

SHOWING 1-10 OF 26 REFERENCES
A high prevalence of HLA-H 845A mutations in hemochromatosis patients and the normal population in eastern England.
TLDR
A snapshot of a relatively stable population containing a predicted 3,500 individuals homozygous for the 845A allele but not diagnosed with hemochromatosis is presented, which will be an excellent model for studies on the penetrance of the 8 45A Homozygous genotype and population screening.
A simple genetic test identifies 90% of UK patients with haemochromatosis
TLDR
These are the first phenotypic observations for patients without either C282Y or H63D mutation of HFE, which promises to be a highly effective tool in the diagnosis of GH.
Mutation analysis of the HLA-H gene in Italian hemochromatosis patients.
TLDR
It is reported that the Cys282Tyr change accounts for 69% of HH chromosomes in a series of 75 unrelated Italian patients who fulfilled well-defined criteria for HH diagnosis, suggesting that in Italy the disease is more heterogeneous than reported in northern Europe.
Global prevalence of putative haemochromatosis mutations.
TLDR
The distribution of the C282Y mutation coincides with that of populations in which haemochromatosis has been reported and is consistent with the theory of a north European origin for the mutation.
Mutation analysis in hereditary hemochromatosis.
TLDR
The DNA of 147 patients of European origin clinically diagnosed with idiopathic hemochromatosis and 193 controls was examined for mutations of the HLA-H gene at nt 845 and nt 187, suggesting the presence of as yet undiscovered mutations existing in trans with 845A and in linkage disequilibrium with 187G.
Haemochromatosis and HLA–H
TLDR
Some of the uncertainty surrounding the role of HLA-H in HH may be resolved by the identification of complete concordance of the C282Y mutation (or some other mutation) in HLA H with disease status in HH families.
Homozygosity for the predominant Cys282Tyr mutation and absence of disease expression in hereditary haemochromatosis.
TLDR
The finding of an asymptomatic homozygous Cys282Tyr subject, haplo-identical to affected sibs, indicates that clinical expression of symptomatic disease is variable, even in middle aged Cys281Tyr homozygotes, which has profound implications for the future use of genetic screening for haemochromatosis.
Clinical and family studies in genetic hemochromatosis: Microsatellite and HFE studies in five atypical families
TLDR
Finding HLA‐identical siblings without iron overload does not confirm a genetic recombination, difficulties in phenotypic definition of disease and the description of new iron overload syndromes that may differ from classical genetic HC cause complicated genetic studies, and finding iron‐loaded patients without a C282y mutation and patients that are homozygous for the C282Y mutation without evidence of iron overload may limit the use of genotyping in population screening for hemochromatosis.
Mutations in the MHC class I-like candidate gene for hemochromatosis in French patients
TLDR
The detection of 845A homozygosity should now permit diagnosis of a readily curable disease and the prevention of sometimes deadly complications in at least 72% of the patients.
The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding.
TLDR
A molecular link between HFE and a key protein involved in iron transport, the TfR, is established and the possibility that alterations in this regulatory mechanism may play a role in the pathogenesis of hereditary hemochromatosis is raised.
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