HFE Genotype and Parameters of Iron Metabolism in German First-Time Blood Donors

Abstract

Background: Hemochromatosis is usually inherited in an autosomal recessive mode and associated with missense mutations in the hemochromatosis gene (HFE), an HLA class 1 related gene. However the degree of penetrance is presently matter of debate.

Methods: To elucidate the frequency of HFE mutations in a German population and the relationship between genotype and phenotype, we determined the HFE C282Y and H63D genotypes in 500 first-time blood donors using an allele-specific ligase chain reaction (LCR). Ferritin and transferrin saturation (TS) of all donors found to have at least one mutation were compared to gender- and age-matched controls.

Results: The C282Y allele frequency was 46 in 1000 chromosomes (4.6 %). The allele frequency of H63D was 108 in 1000 (10.8 %) chromosomes. We found three persons homozygous for H63D, nine compound heterozygotes and none homozygous for C282Y. TS was elevated in C282Y heterozygotes (p = 0.002) and C282Y/H63D compound heterozygotes (p = 0.04) compared to wild-type controls. Serum ferritin tended to be elevated in compound heterozygotes (p = 0.053). Mean corpuscular volume (MCV) and hemoglobin (MCH) were not different from controls.

Conclusion: The frequency of HFE mutations in the tested population was comparable to those of other northern European populations. 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.

Zusammenfassung

Die hereditäre Hämochromatose ist eine autosomal rezessiv vererbbare Störung des Eisenstoffwechsels, die mit Mutationen im Hämochromatosegen (HFE), einem HLA-Klasse-1-ähnlichen Gen einhergeht. Das Ausmaß der Penetranz der Erkrankung wird gegenwärtig kontrovers diskutiert.

Methoden: 500 Erstblutspender wurden im Hinblick auf das Vorliegen der HFE-C282Y- und H63D-Mutation mithilfe einer allelspezifischen Ligasekettenreaktion untersucht. Ferritin und die Transferrinsättigung (TS) von Spendern, bei denen sich mindestens eine Mutation nachweisen ließ, wurden mit den Eisenstoffwechselparametern eines alters- und geschlechtsnormalisierten Kontrollkollektivs verglichen.

Ergebnisse: Die C282Y-Mutation wurde bei 46 von 1000 (4,6 %), die H63D-Mutation in 108 von 1000 (10,8 %) untersuchten Chromosomen festgestellt. Drei Spender waren H63D-homozygot, neun waren C282Y/H63D-compound-heterozygot. Keiner der Spender war C282Y-homozygot. Bei C282Y-heterozygoten und C282Y/H63D-compound-heterozygoten Individuen war die TS gegenüber den Kontrollkollektiven signifikant erhöht (p = 0,002 bzw. 0,04). Bei C282Y/H63D-compound-heterozygoten Spendern zeigte sich tendenziell ein erhöhter Ferritinspiegel (p = 0,053). Es zeigten sich keine Unterschiede im Hinblick auf das mittlere Erythrozytenvolumen (MCV) und den mittleren erythrozytären Hämoglobingehalt (MCH).

Diskussion: Die HFE-Allelfrequenz im untersuchten Kollektiv entspricht im Wesentlichen der anderer nordeuropäischer Populationen. Heterozygote Träger einer C282Y-Mutation haben eine erhöhte TS als Ausdruck einer vermehrten Eisenaufnahme. Dies ist möglicherweise Ausdruck eines Selektionsvorteils in Zeiten eines Eisenmangels.

Hemochromatosis - HFE - transferrin saturation - ferritin

Hämochromatose - HFE - Transferrinsättigung - Ferritin

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