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An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1α) Polymorphisms and Osteonecrosis
Bone hypoxia resulting from impaired blood flow is the final pathway for the development of osteonecrosis (ON). The aim of this study was to evaluate if HIF-1α, the major transcription factor triggered by hypoxia, is genetically implicated in susceptibility to ON. For this we analyzed frequencies of...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832621/ https://www.ncbi.nlm.nih.gov/pubmed/24260273 http://dx.doi.org/10.1371/journal.pone.0079647 |
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author | Chachami, Georgia Kalousi, Alkmini Papatheodorou, Loukia Lyberopoulou, Aggeliki Nasikas, Vasileios Tanimoto, Keiji Simos, George Malizos, Konstantinos N. Georgatsou, Eleni |
author_facet | Chachami, Georgia Kalousi, Alkmini Papatheodorou, Loukia Lyberopoulou, Aggeliki Nasikas, Vasileios Tanimoto, Keiji Simos, George Malizos, Konstantinos N. Georgatsou, Eleni |
author_sort | Chachami, Georgia |
collection | PubMed |
description | Bone hypoxia resulting from impaired blood flow is the final pathway for the development of osteonecrosis (ON). The aim of this study was to evaluate if HIF-1α, the major transcription factor triggered by hypoxia, is genetically implicated in susceptibility to ON. For this we analyzed frequencies of three known HIF-1α polymorphisms: one in exon 2 (C111A) and two in exon 12 (C1772T and G1790A) and their association with ON in a Greek population. Genotype analysis was performed using PCR-RFLP and rare alleles were further confirmed with sequencing. We found that genotype and allele frequency of C1772T and G1790A SNP of HIF-1α (SNPs found in our cohort) were not significantly different in ON patients compared to control patients. Furthermore these SNPs could not be associated with the different subgroups of ON. At the protein level we observed that the corresponding mutations (P582S and A588T, respectively) are not significant for protein function since the activity, expression and localization of the mutant proteins is practically indistinguishable from wt in HEK293 and Saos-2 cells. These results suggest that these missense mutations in the HIF-1α gene are not important for the risk of developing ON. |
format | Online Article Text |
id | pubmed-3832621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38326212013-11-20 An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1α) Polymorphisms and Osteonecrosis Chachami, Georgia Kalousi, Alkmini Papatheodorou, Loukia Lyberopoulou, Aggeliki Nasikas, Vasileios Tanimoto, Keiji Simos, George Malizos, Konstantinos N. Georgatsou, Eleni PLoS One Research Article Bone hypoxia resulting from impaired blood flow is the final pathway for the development of osteonecrosis (ON). The aim of this study was to evaluate if HIF-1α, the major transcription factor triggered by hypoxia, is genetically implicated in susceptibility to ON. For this we analyzed frequencies of three known HIF-1α polymorphisms: one in exon 2 (C111A) and two in exon 12 (C1772T and G1790A) and their association with ON in a Greek population. Genotype analysis was performed using PCR-RFLP and rare alleles were further confirmed with sequencing. We found that genotype and allele frequency of C1772T and G1790A SNP of HIF-1α (SNPs found in our cohort) were not significantly different in ON patients compared to control patients. Furthermore these SNPs could not be associated with the different subgroups of ON. At the protein level we observed that the corresponding mutations (P582S and A588T, respectively) are not significant for protein function since the activity, expression and localization of the mutant proteins is practically indistinguishable from wt in HEK293 and Saos-2 cells. These results suggest that these missense mutations in the HIF-1α gene are not important for the risk of developing ON. Public Library of Science 2013-11-18 /pmc/articles/PMC3832621/ /pubmed/24260273 http://dx.doi.org/10.1371/journal.pone.0079647 Text en © 2013 Chachami et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chachami, Georgia Kalousi, Alkmini Papatheodorou, Loukia Lyberopoulou, Aggeliki Nasikas, Vasileios Tanimoto, Keiji Simos, George Malizos, Konstantinos N. Georgatsou, Eleni An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1α) Polymorphisms and Osteonecrosis |
title | An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1α) Polymorphisms and Osteonecrosis |
title_full | An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1α) Polymorphisms and Osteonecrosis |
title_fullStr | An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1α) Polymorphisms and Osteonecrosis |
title_full_unstemmed | An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1α) Polymorphisms and Osteonecrosis |
title_short | An Association Study between Hypoxia Inducible Factor-1alpha (HIF-1α) Polymorphisms and Osteonecrosis |
title_sort | association study between hypoxia inducible factor-1alpha (hif-1α) polymorphisms and osteonecrosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832621/ https://www.ncbi.nlm.nih.gov/pubmed/24260273 http://dx.doi.org/10.1371/journal.pone.0079647 |
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