Distribution of HFE Gene Variants in Patients Undergoing Genetic Testing in Türkiye: A Retrospective Analysis of 643...

Hereditary hemochromatosis (HH) is a common genetic disorder of iron metabolism, most frequently associated with pathogenic variants in the HFE gene. The distribution of HFE variants shows marked population-specific differences. This study aimed to evaluate the frequency and genotype distribution of major HFE variants in a large Turkish cohort.

A total of 643 patients who underwent HFE gene sequencing at a single tertiary center were retrospectively analyzed. Genotype and allele frequencies of common HFE variants, including p.Cys282Tyr, p.His63Asp, and p.Ser65Cys, as well as rare variants were calculated. Clinical and biochemical parameters were not included, and the analysis focused exclusively on genetic frequency data.

Among the 643 patients, 424 (65.9%) were wild-type for HFE. The most frequent variant was H63D heterozygosity, detected in 166 patients (25.8%). p.Cys282Tyr homozygosity was identified in only 4 patients (0.6%). Compound heterozygosity for p.Cys282Tyr and p.His63Asp was observed in 1 patient, while another patient showed homozygous His63Asp with heterozygous p.Arg224Trp. In terms of allele frequencies, p.His63Asp was the most common with 0.183, followed by p.Cys282Tyr with a frequency of 0.012.

The findings demonstrate a distinct HFE genetic profile in the Turkish population, characterized by a low frequency of p.Cys282Tyr and a high prevalence of p.His63Asp heterozygosity. These results highlight the importance of population-specific genetic data for accurate interpretation of HFE testing and HH risk assessment. Cite this article as: Kablan A, Sezer A, Bakır A, et al. Distribution of HFE gene variants in patients undergoing genetic testing in Türkiye: A retrospective analysis of 643 cases. Eurasian J Med. 2026, 58(3), 1390, doi: 10.5152/eurasianjmed.2026.261390.