Prevalence of the H63D and C282Y Mutations in the HFE Gene in 3,015 Blood Donors from Southwestern Germany

Abstract

Background: Hereditary haemochromatosis (HH) is the most common genetic disease with a prevalence of 1:200–1:400 in Northern Europe. In most cases HH is caused by two mutations of the HFE gene (H63D and C282Y). As haemochromatosis leads to elevated iron uptake it is conceivable that blood donors with HFE mutation might be refused from giving a donation less often than donors without the mutation. Therefore, HFE mutations might be overrepresented among frequent blood donors. This study aimed to determine the prevalence of HFE mutations in a blood donor population from Southwestern Germany. Material and Methods: The HFE mutations H63D and C282Y were analysed in 3,015 samples by PCR-SSP typing. Age and sex of the donors were considered as well as the number of blood donations. Results: No differences in frequency of both mutations could be observed between first-time and frequent donors. The prevalence of the H63D mutations was higher among female than male donors: 28.6 vs. 24.3%; p = 0.007, whereas the genotype frequencies containing the C282Y mutation were similar between male and female donors. Compared to populations from Australia or South Wales the prevalence of the C282Y mutation was lower in our blood donor population (14.8–15.8 vs. 9.0%; p < 0,0001). Conclusions: The proposed overrepresentation of HFE mutations among frequent donors could not be confirmed. However, we found a higher prevalence of the H63D mutation in female donors than in male donors. One might therefore presume that blood donation in addition to the loss of blood due to menstruation is compensated more adequately in female H63D mutation carriers than in females without H63D mutation. This mutation seems to elevate the iron uptake so that female mutation carriers may have a higher chance to be admitted for blood donation. Individuals with diagnosed haemochromatosis-linked mutations should be informed about the potential health benefit from periodical blood donation and the admittance of such donors should be considered in Germany.

The impact of HFE mutations on haemoglobin and iron status in individuals experiencing repeated iron loss through blood donation*

“…However, even in the large population of donors studied here, the prevalence of donors with HFE mutations was not different among the high intensity and lower intensity donors. This finding is consistent with previously published studies of smaller numbers of donors (Konig et al, 2003;Boulton et al, 2000) and confirms that it is unlikely that these mutations are responsible for potential genetic contributions to the ability of high intensity donors to repeatedly donate blood without developing iron deficiency anaemia. Another mutation studied in RISE is TF G227S.…”

“…Although the C282Y mutation has a greater impact on iron balance than H63D, high intensity donors that carry the H63D mutation have decreased hepcidin to ferritin ratios when compared to those without the mutation (Mast et al , 2008a). A separate study found that the prevalence of H63D was higher among female than male donors (Konig et al , 2003). These data suggest that carriers of H63D may absorb more dietary iron when iron stores are depleted than those without the mutation, potentially protecting them from blood donation‐induced iron deficiency anaemia.…”

“…These data suggest that carriers of H63D may absorb more dietary iron when iron stores are depleted than those without the mutation, potentially protecting them from blood donationinduced iron deficiency anaemia. Despite these findings, several studies have determined that the prevalence of carriers for HFE mutations in high intensity blood donors is similar to the general population, rather than increased, as would be expected, if these mutations allowed individuals to repeatedly donate blood without development of anaemia (Mast et al, 2008a;Konig et al, 2003;Boulton et al, 2000).…”

Genetic and behavioral modification of hemoglobin and iron status among first‐time and high‐intensity blood donors

“…This was somewhat surprising, since C282Y is more strongly associated with hemochromatosis . However, previous studies have found a protective association of H63D, but not C282Y, on iron status in frequent donors . For example, H63D is fourfold more prevalent in frequent Black donors than in first‐time Black donors .…”

“…28 However, previous studies have found a protective association of H63D, but not C282Y, on iron status in frequent donors. 29 For example, H63D is fourfold more prevalent in frequent Black donors than in first-time Black donors. 9 And, in a population of high-intensity donors, those with H63D had decreased hepcidin:ferritin ratio compared to those without this mutation.…”