Open AccessDCTN 4 as a modifier of chronic P seudomonas aeruginosa infection in cystic fibrosis
Author(s) -
Viel Marion,
Hubert Dominique,
Burgel PierreRegis,
Génin Emmanuelle,
Honoré Isabelle,
Martinez Brigitte,
Gaitch Natacha,
Chapron Jeanne,
Kanaan Reem,
Dusser Daniel,
Girodon Emmanuelle,
Bienvenu Thierry
Publication year - 2016
Publication title -
the clinical respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.789
H-Index - 33
eISSN - 1752-699X
pISSN - 1752-6981
DOI - 10.1111/crj.12288
Subject(s) - medicine , cystic fibrosis , missense mutation , exome sequencing , gastroenterology , incidence (geometry) , chronic infection , immunology , phenotype , gene , biology , genetics , immune system , physics , optics
Background and Aims P seudomonas aeruginosa ( Pa ) infection in cystic fibrosis ( CF ) patients is associated with worse long‐term pulmonary disease and shorter survival, and chronic Pa infection ( CPA ) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 ( DCTN 4) may influence Pa infection in CF , leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN 4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre. Methods Polymerase chain reaction and direct sequencing were used to screen DNA samples for DCTN 4 variants. Results A total of 121 adult CF patients from the C ochin H ospital CF centre have been included, all of them carrying two CFTR defects: 103 developed at least 1 pulmonary infection with Pa , and 68 patients of them had CPA . DCTN 4 variants were identified in 24% (29/121) CF patients with Pa infection and in only 17% (3/18) CF patients with no P a infection. Of the patients with CPA , 29% (20/68) had DCTN 4 missense variants vs 23% (8/35) in patients without CPA . Interestingly, p. Tyr 263 Cys tend to be more frequently observed in CF patients with CPA than in patients without CPA (4/68 vs 0/35), and DCTN 4 missense variants tend to be more frequent in male CF patients with CPA bearing two class II mutations than in male CF patients without CPA bearing two class II mutations ( P = 0.06).Conclusions Our observations reinforce that DCTN 4 missense variants, especially p. Tyr 263 Cys , may be involved in the pathogenesis of CPA in male CF .