Hemochromatosis gene HFE Cys282Tyr mutation analysis in a cohort of Northeast German hospitalized patients supports assumption of a North to South allele frequency gradient throughout Germany

Abstract

Hereditary hemochromatosis is the most common autosomal recessive disease in populations of Northern European ancestry. Population studies demonstrated highly variable frequencies of the HFE Cys282Tyr allele in various regions throughout Europe and decreasing allele frequencies from north to south. However, most of the German prevalence studies covered the central and southern regions of the country. The present study recruited 709 consecutive patients at the time of their admission to a Northeast German University Hospital Medical Department. Polymerase chain reaction-based assays were used to detect HFE Cys282Tyr and His63Asp alleles. Biochemical profiling consisting of transferrin saturation rate, and concentrations of ferritin, transferrin, and iron were performed in Cys282Tyr homozygotes and Cys282Tyr/His63Asp heterozygotes, respectively. Results were compared with previous German prevalence studies. Analysis of 709 Caucasian patients resulted in 650 (91.7%) homozygous HFE wild-type carriers, 55 (7.74%) Cys282Tyr heterozygotes, 4 (0.56%) Cys282Tyr homozygotes and 6 (0.85%) Cys282Tyr/His63Asp compound heterozygotes. The HFE Cys282Tyr allele frequency was 4.44%. Phenotypic markers of iron overload were elevated in one homozygote. We conclude that in contrast to previous hemochromatosis prevalence studies in Germany using blood donors or employees, the present study involving hospital patients estimated a HFE Cys282Tyr allele frequency of 4.44% and supports the emerging concept of an allele gradient decreasing from North to South within Germany.