Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease
The severity of cystic fibrosis (CF) pulmonary disease is not directly related to CFTR genotype but depends upon several parameters, including neutrophil-dominated inflammation. Identification of agents modulating inflammation constitutes a relevant goal. Myeloperoxidase (MPO) is involved in both mi...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2006-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/MI/2006/36735 |
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| _version_ | 1832567290219986944 |
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| author | Wanda F. Reynolds Isabelle Sermet-Gaudelus Valérie Gausson Marie-Noëlle Feuillet Jean-Paul Bonnefont Gérard Lenoir Béatrice Descamps-Latscha Véronique Witko-Sarsat |
| author_facet | Wanda F. Reynolds Isabelle Sermet-Gaudelus Valérie Gausson Marie-Noëlle Feuillet Jean-Paul Bonnefont Gérard Lenoir Béatrice Descamps-Latscha Véronique Witko-Sarsat |
| author_sort | Wanda F. Reynolds |
| collection | DOAJ |
| description | The severity of cystic fibrosis (CF) pulmonary disease is not directly related to CFTR genotype but depends upon several parameters, including neutrophil-dominated inflammation. Identification of agents modulating inflammation constitutes a relevant goal. Myeloperoxidase (MPO) is involved in both microbicidal and proinflammatory neutrophil activities. The aim of this study was to evaluate whether the −463GA MPO promoter polymorphism is linked to clinical severity of CF-associated pulmonary inflammation. This polymorphism significantly affects the level of MPO gene expression in leukocytes and the G allele is more expressing than the A allele. We show that MPO genotype significantly influences the severity of pulmonary disease in early stages, prior to the development of chronic lung infections, with GG genotype being associated with more severe CF disease. Our findings indicate that the level of MPO gene expression influences the CF pathogenesis, presumably reflecting cellular damage by MPO-generated oxidants or other activity of MPO in airway inflammation. |
| format | Article |
| id | doaj-art-1f07d9e8142449b582aab4e8004198b2 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2006-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1f07d9e8142449b582aab4e8004198b22025-02-03T01:01:48ZengWileyMediators of Inflammation0962-93511466-18612006-01-01200610.1155/MI/2006/3673536735Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary DiseaseWanda F. Reynolds0Isabelle Sermet-Gaudelus1Valérie Gausson2Marie-Noëlle Feuillet3Jean-Paul Bonnefont4Gérard Lenoir5Béatrice Descamps-Latscha6Véronique Witko-Sarsat7Sidney Kimmel Cancer Center, San Diego, CA 92121, USAService de Pédiatrie Générale, Hôpital Necker-Enfants Malades, Paris 75015, FranceINSERM U507, Hôpital Necker-Enfants Malades, Paris 75015, FranceService de Biochimie B, Hôpital Necker-Enfants Malades, Paris 75015, FranceService de Biochimie B, Hôpital Necker-Enfants Malades, Paris 75015, FranceService de Pédiatrie Générale, Hôpital Necker-Enfants Malades, Paris 75015, FranceINSERM U507, Hôpital Necker-Enfants Malades, Paris 75015, FranceINSERM U507, Hôpital Necker-Enfants Malades, Paris 75015, FranceThe severity of cystic fibrosis (CF) pulmonary disease is not directly related to CFTR genotype but depends upon several parameters, including neutrophil-dominated inflammation. Identification of agents modulating inflammation constitutes a relevant goal. Myeloperoxidase (MPO) is involved in both microbicidal and proinflammatory neutrophil activities. The aim of this study was to evaluate whether the −463GA MPO promoter polymorphism is linked to clinical severity of CF-associated pulmonary inflammation. This polymorphism significantly affects the level of MPO gene expression in leukocytes and the G allele is more expressing than the A allele. We show that MPO genotype significantly influences the severity of pulmonary disease in early stages, prior to the development of chronic lung infections, with GG genotype being associated with more severe CF disease. Our findings indicate that the level of MPO gene expression influences the CF pathogenesis, presumably reflecting cellular damage by MPO-generated oxidants or other activity of MPO in airway inflammation.http://dx.doi.org/10.1155/MI/2006/36735 |
| spellingShingle | Wanda F. Reynolds Isabelle Sermet-Gaudelus Valérie Gausson Marie-Noëlle Feuillet Jean-Paul Bonnefont Gérard Lenoir Béatrice Descamps-Latscha Véronique Witko-Sarsat Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease Mediators of Inflammation |
| title | Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease |
| title_full | Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease |
| title_fullStr | Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease |
| title_full_unstemmed | Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease |
| title_short | Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease |
| title_sort | myeloperoxidase promoter polymorphism 463g is associated with more severe clinical expression of cystic fibrosis pulmonary disease |
| url | http://dx.doi.org/10.1155/MI/2006/36735 |
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