Mediators of Inflammation 
Volume 2006 (2006), Article ID 36735, 8 pages
doi:10.1155/MI/2006/36735
Research Communication

Myeloperoxidase Promoter Polymorphism −463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease

Wanda F. Reynolds,1 Isabelle Sermet-Gaudelus,2 Valérie Gausson,3 Marie-Noëlle Feuillet,4 Jean-Paul Bonnefont,4 Gérard Lenoir,2 Béatrice Descamps-Latscha,3 and Véronique Witko-Sarsat3

 1Sidney Kimmel Cancer Center, San Diego 92121, CA, USA
2Service de Pédiatrie Générale, Hôpital Necker-Enfants Malades, Paris 75015, France
3INSERM U507, Hôpital Necker-Enfants Malades, Paris 75015, France
4Service de Biochimie B, Hôpital Necker-Enfants Malades, Paris 75015, France
Received 24 November 2005; Accepted 30 November 2005

Abstract

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.