Synergistic Contribution of HFE H63D Mutation to Secondary Polycythemia Pathogenesis at Moderate-High Altitude: A Retrospective Cohort Study

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Cinli T. A., Alavanda C.

DIAGNOSTICS, cilt.16, sa.13, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 16 Sayı: 13
  • Basım Tarihi: 2026
  • Doi Numarası: 10.3390/diagnostics16132087
  • Dergi Adı: DIAGNOSTICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO)
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • İstanbul Üniversitesi Adresli: Evet

Özet

Objective: This study examined whether HFE H63D carriers living at moderate-to-high altitude have a stronger secondary polycythemia phenotype than non-carriers from the same region. Methods: This retrospective cohort study included 59 patients with HFE gene mutation (heterozygous n = 49, homozygous n = 10) and 51 controls without HFE mutation (total N = 110). JAK2 V617F negativity was confirmed in all participants. Serum erythropoietin (EPO) levels were assessed in the HFE mutation group to support secondary, non-clonal erythrocytosis. Results: Hemoglobin (17.32 +/- 1.29 vs. 15.11 +/- 0.95 g/dL (p < 0.001), hematocrit (median 51.50 vs. 45.20; p < 0.001), and erythrocyte count (p < 0.001) were significantly higher in the HFE mutation group. Transferrin saturation was higher in the HFE mutation group than in controls (64.56 +/- 2.03% vs. 36.30 +/- 1.58%; p < 0.001; Cohen's d = 0.95). Serum iron was higher and total iron-binding capacity was lower in the HFE mutation group, respectively (127.58 +/- 44.10 vs. 93.62 +/- 29.55 & micro;g/dL and 194.32 +/- 72.41 vs. 243.36 +/- 40.82 & micro;g/dL; both p < 0.001). CRP levels were also significantly elevated (p < 0.001). No significant differences were observed between the heterozygous and homozygous HFE mutation subgroup. Conclusions: HFE H63D carriers had higher erythrocytosis-related parameters and transferrin saturation than controls. These findings suggest that HFE-related changes in iron handling may strengthen the erythrocytosis phenotype at moderate-to-high altitude. Larger prospective studies should test this association.