HFE-Related Hemochromatosis: The Haptoglobin 2-2 Type Has a Significant but Limited Influence on Phenotypic Expression of the Predominant p.C282Y Homozygous Genotype
Phenotypic expression of the common p.C282Y/p.C282Y HFE-related hemochromatosis genotype is heterogeneous and depends on a complex interplay of genetic and non-genetic factors. Haptoglobin has a crucial role in free hemoglobin iron recovery, and exists as three major types: Hp1-1, Hp2-1 and Hp2-2. H...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2009-01-01
|
| Series: | Advances in Hematology |
| Online Access: | http://dx.doi.org/10.1155/2009/251701 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832567846781059072 |
|---|---|
| author | Gérald Le Gac Chandran Ka Isabelle Gourlaouen Laurence Bryckaert Anne-Yvonne Mercier Brigitte Chanu Virginie Scotet Claude Férec |
| author_facet | Gérald Le Gac Chandran Ka Isabelle Gourlaouen Laurence Bryckaert Anne-Yvonne Mercier Brigitte Chanu Virginie Scotet Claude Férec |
| author_sort | Gérald Le Gac |
| collection | DOAJ |
| description | Phenotypic expression of the common p.C282Y/p.C282Y HFE-related hemochromatosis genotype is heterogeneous and depends on a complex interplay of genetic and non-genetic factors. Haptoglobin has a crucial role in free hemoglobin iron recovery, and exists as three major types: Hp1-1, Hp2-1 and Hp2-2. Hp2-2 favors endocytosis of hemoglobin iron in monocytes/macrophages, resulting in partial iron retention and increased intracellular ferritin levels. This situation is generally not expected to severely affect iron homeostasis, but was found to correlate with elevated serum iron indices in healthy men. Whether the Hp2-2 genotype acts as a modifier in HFE-related hemochromatosis is unclear.
In this study we investigated influence of Hp2-2 and of potential confounders on the iron indices of 351 p.C282Y homozygous patients. We conclude that there is a cause-and-effect relationship between the Hp2-2 genotype and increased iron indices in p.C282Y homozygous patients. The Hp2-2 effect is, however, limited and only apparent in males. |
| format | Article |
| id | doaj-art-1d04a980845e43e5937a93d84b644675 |
| institution | Kabale University |
| issn | 1687-9104 1687-9112 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Hematology |
| spelling | doaj-art-1d04a980845e43e5937a93d84b6446752025-02-03T01:00:14ZengWileyAdvances in Hematology1687-91041687-91122009-01-01200910.1155/2009/251701251701HFE-Related Hemochromatosis: The Haptoglobin 2-2 Type Has a Significant but Limited Influence on Phenotypic Expression of the Predominant p.C282Y Homozygous GenotypeGérald Le Gac0Chandran Ka1Isabelle Gourlaouen2Laurence Bryckaert3Anne-Yvonne Mercier4Brigitte Chanu5Virginie Scotet6Claude Férec7 Etablissement Français du Sang Bretagne, Brest 29200, France Etablissement Français du Sang Bretagne, Brest 29200, France Etablissement Français du Sang Bretagne, Brest 29200, France Etablissement Français du Sang Bretagne, Brest 29200, France Etablissement Français du Sang Bretagne, Brest 29200, France Etablissement Français du Sang Bretagne, Brest 29200, France Etablissement Français du Sang Bretagne, Brest 29200, France Etablissement Français du Sang Bretagne, Brest 29200, FrancePhenotypic expression of the common p.C282Y/p.C282Y HFE-related hemochromatosis genotype is heterogeneous and depends on a complex interplay of genetic and non-genetic factors. Haptoglobin has a crucial role in free hemoglobin iron recovery, and exists as three major types: Hp1-1, Hp2-1 and Hp2-2. Hp2-2 favors endocytosis of hemoglobin iron in monocytes/macrophages, resulting in partial iron retention and increased intracellular ferritin levels. This situation is generally not expected to severely affect iron homeostasis, but was found to correlate with elevated serum iron indices in healthy men. Whether the Hp2-2 genotype acts as a modifier in HFE-related hemochromatosis is unclear. In this study we investigated influence of Hp2-2 and of potential confounders on the iron indices of 351 p.C282Y homozygous patients. We conclude that there is a cause-and-effect relationship between the Hp2-2 genotype and increased iron indices in p.C282Y homozygous patients. The Hp2-2 effect is, however, limited and only apparent in males.http://dx.doi.org/10.1155/2009/251701 |
| spellingShingle | Gérald Le Gac Chandran Ka Isabelle Gourlaouen Laurence Bryckaert Anne-Yvonne Mercier Brigitte Chanu Virginie Scotet Claude Férec HFE-Related Hemochromatosis: The Haptoglobin 2-2 Type Has a Significant but Limited Influence on Phenotypic Expression of the Predominant p.C282Y Homozygous Genotype Advances in Hematology |
| title | HFE-Related Hemochromatosis: The Haptoglobin 2-2 Type Has a Significant but Limited Influence on Phenotypic Expression of the Predominant p.C282Y Homozygous Genotype |
| title_full | HFE-Related Hemochromatosis: The Haptoglobin 2-2 Type Has a Significant but Limited Influence on Phenotypic Expression of the Predominant p.C282Y Homozygous Genotype |
| title_fullStr | HFE-Related Hemochromatosis: The Haptoglobin 2-2 Type Has a Significant but Limited Influence on Phenotypic Expression of the Predominant p.C282Y Homozygous Genotype |
| title_full_unstemmed | HFE-Related Hemochromatosis: The Haptoglobin 2-2 Type Has a Significant but Limited Influence on Phenotypic Expression of the Predominant p.C282Y Homozygous Genotype |
| title_short | HFE-Related Hemochromatosis: The Haptoglobin 2-2 Type Has a Significant but Limited Influence on Phenotypic Expression of the Predominant p.C282Y Homozygous Genotype |
| title_sort | hfe related hemochromatosis the haptoglobin 2 2 type has a significant but limited influence on phenotypic expression of the predominant p c282y homozygous genotype |
| url | http://dx.doi.org/10.1155/2009/251701 |
| work_keys_str_mv | AT geraldlegac hferelatedhemochromatosisthehaptoglobin22typehasasignificantbutlimitedinfluenceonphenotypicexpressionofthepredominantpc282yhomozygousgenotype AT chandranka hferelatedhemochromatosisthehaptoglobin22typehasasignificantbutlimitedinfluenceonphenotypicexpressionofthepredominantpc282yhomozygousgenotype AT isabellegourlaouen hferelatedhemochromatosisthehaptoglobin22typehasasignificantbutlimitedinfluenceonphenotypicexpressionofthepredominantpc282yhomozygousgenotype AT laurencebryckaert hferelatedhemochromatosisthehaptoglobin22typehasasignificantbutlimitedinfluenceonphenotypicexpressionofthepredominantpc282yhomozygousgenotype AT anneyvonnemercier hferelatedhemochromatosisthehaptoglobin22typehasasignificantbutlimitedinfluenceonphenotypicexpressionofthepredominantpc282yhomozygousgenotype AT brigittechanu hferelatedhemochromatosisthehaptoglobin22typehasasignificantbutlimitedinfluenceonphenotypicexpressionofthepredominantpc282yhomozygousgenotype AT virginiescotet hferelatedhemochromatosisthehaptoglobin22typehasasignificantbutlimitedinfluenceonphenotypicexpressionofthepredominantpc282yhomozygousgenotype AT claudeferec hferelatedhemochromatosisthehaptoglobin22typehasasignificantbutlimitedinfluenceonphenotypicexpressionofthepredominantpc282yhomozygousgenotype |