ABCB6 polymorphisms are not overly represented in patients with porphyria
| Autor: | Jérôme Lamoril, Dimitri Tchernitchko, Robert J. Desnick, Charles J. Parker, Hervé Puy, Laurent Gouya, Brenden Chen, Zoubida Karim, Gaël Nicolas, Colin P. Farrell, John D. Phillips |
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| Přispěvatelé: | Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Excellence Gr-Ex (Labex Gr-Ex) and the Institut National de la Santé et de la Recherche Medicale (INSERM).The Labex GR-Ex is funded by the program 'Investissements d’avenir' of the French National Research Agency, reference ANR-11-IDEX-0005-02. |
| Rok vydání: | 2022 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities acute hepatic porphyria Protoporphyria Erythropoietic erythropoietic protoporphyria Variegate porphyria Biology Mice Porphyrias 03 medical and health sciences chemistry.chemical_compound medicine Animals Humans [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] heme skin and connective tissue diseases Heme 030304 developmental biology Acute intermittent porphyria Mice Knockout Genetics 0303 health sciences Genetic heterogeneity 030305 genetics & heredity nutritional and metabolic diseases Porphobilinogen Synthase [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology Hematology [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ABCB6 medicine.disease Penetrance Porphyrias Hepatic 3. Good health Hereditary coproporphyria Porphyria [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics chemistry ATP-Binding Cassette Transporters Erythropoietic protoporphyria [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition |
| Zdroj: | Blood Advances Blood Advances, The American Society of Hematology, 2021, ⟨10.1182/bloodadvances.2021005484⟩ |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2021005484 |
| Popis: | The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted. |
| Databáze: | OpenAIRE |
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