Myeloperoxidase Promoter Polymorphism <mml:math alttext="$\boldsymbol{-}$" id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>−</mml:mo></mml:math>463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease

Reynolds, Wanda F.; Sermet-Gaudelus, Isabelle; Gausson, Valérie; Feuillet, Marie-Noëlle; Bonnefont, Jean-Paul; Lenoir, Gérard; Descamps-Latscha, Béatrice; Witko-Sarsat, Véronique

doi:https://doi.org/10.1155/MI/2006/36735

Mediators of Inflammation

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Research Communication | Open Access

Volume 2006 | Article ID 036735 | https://doi.org/10.1155/MI/2006/36735

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

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

Received24 Nov 2005

Accepted30 Nov 2005

Published13 Mar 2006

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.

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Copyright © 2006 Wanda F. Reynolds et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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