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

Abstract

Summary. High frequencies of the haemochromatosisrelated 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 chromosomes, indicating a homozygote frequency of 1/145. Consistent with this, four C282Y homozygotes were detected in 411 volunteers. As there are only 18 patients presently receiving treatment for haemochromatosis on Jersey, out of a total population of about 85 000, there is a large discrepancy between the number of haemochromatosis patients and the number of C282Y homozygotes in this population. In a preliminary study of 204 consenting volunteers we found a correlation between transferrin saturation and HFE H63D/ C282Y genotype (P ¼ 0·017) and between serum ferritin and genotype (P ¼ 0·056). We also observed elevated values of transferrin saturation in the two C282Y homozygotes assayed. These results suggest that a large proportion of the many undetected C282Y homozygotes on Jersey and in similar populations could be in the preclinical stages of haemochromatosis, and warrant investigation. However, there may be a wide variation in the expression of the condition, and a more extensive study of the level of disease penetrance encompassing a large number of hitherto undetected C282Y homozygotes is therefore imperative.

Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation

“…Merryweather-Clarke and colleagues 67 reported a population prevalence for haemochromatosis of 1 in 4700 in Jersey. Other studies have presented prevalence rates for specific groups who have presented with different signs and symptoms characteristic of increased iron.…”

“…38,62 The other two studies were a retrospective cohort study 13 and a cross-sectional case-control study. 64 The participants in the studies varied depending upon the rationale for the study, including people diagnosed with haemochromatosis, 13,38,62 people attending a blood donation service, 65,67 those on registers of newborn children 63 or heart attack sufferers, 64 and those attending for routine blood screening. 66 Control groups included healthy blood donors, 38 people registered with general practitioners 64 and people on bone marrow registers.…”

“…13,38,[62][63][64][65][66][67] Six studies were prospective cohort studies, 38,62,63,[65][66][67] with two including a control group. 38,62 The other two studies were a retrospective cohort study 13 and a cross-sectional case-control study.…”

“…In the UK studies identified, the prevalence of the C282Y homozygous mutation in the general population ranged from 0.68% 65 to 1.24%, 62 with five studies identifying prevalence rates between 0.9% and 1% (median prevalence 0.97%). 38,63,64,66,67 Prevalence rates in the UK for the C282Y heterozygous mutation were higher and had a wider range. The prevalence in the five studies ranged from 5.9% in a cohort of healthy blood donors 38 to 19% in a cohort of newborn Irish children.…”

“…Prevalence data for the general population originated from several cohorts including healthy blood donors, 38,65,67 a register of newborn children, 63 general practitioner populations, 64 people on bone marrow registers 62 and people providing blood specimens for routine screening. 66 Inevitably the variations in these groups may have some effect on the prevalence rates reported.…”