Open AccessCytokine and Gene Expression Profiling in Patients with <b><i>HFE</i></b>-Associated Hereditary Hemochromatosis according to Genetic Profile
Author(s) -
Heidi Kristine Grønlien,
Trine Eker Christoffersen,
Camilla Furlund Nystrand,
Lamya Garabet,
Terje Syvertsen,
Morten K. Moe,
Ole Kristoffer Olstad,
Christine Monceyron Jonassen
Publication year - 2020
Publication title -
acta haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 56
eISSN - 1421-9662
pISSN - 0001-5792
DOI - 10.1159/000511551
Subject(s) - hepcidin , hereditary hemochromatosis , hemochromatosis , medicine , cytokine , inflammation , gene expression , endocrinology , immunology , biology , gene , genetics
Background: Hemochromatosis gene ( HFE )-associated hereditary hemochromatosis (HH) is characterized by downregulation of hepcidin synthesis, leading to increased intestinal iron absorption. Objectives: The objectives were to characterize and elucidate a possible association between gene expression profile, hepcidin levels, disease severity, and markers of inflammation in HFE -associated HH patients. Methods: Thirty-nine HFE -associated HH patients were recruited and assigned to 2 groups according to genetic profile: C282Y homozygotes in 1 group and patients with H63D, as homozygote or in combination with C282Y, in the other group. Eleven healthy first-time blood donors were recruited as controls. Gene expression was characterized from peripheral blood cells, and inflammatory cytokines and hepcidin-25 isoform were quantified in serum. Biochemical disease characteristics were recorded. Results: Elevated levels of interleukin 8 were observed in a significant higher proportion of patients than controls. In addition, compared to controls, gene expression of ζ-globin was significantly increased among C282Y homozygote patients, while gene expression of matrix metalloproteinase 8, and other neutrophil-secreted proteins, was significantly upregulated in patients with H63D. Conclusion: Different disease signatures may characterize HH patients according to their HFE genetic profile. Studies on larger populations, including analyses at protein level, are necessary to confirm these findings.