Mannose-binding lectin gene as a modifier of the cystic fibrosis phenotype in Argentinean pediatric patients

  • Luis Pablo Gravina
    Affiliations
    Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires, Argentina
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  • Carolina Crespo
    Affiliations
    Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires, Argentina
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  • Hilda Giugno
    Affiliations
    Servicio de Neumonología, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires, Argentina
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  • Luisa Sen
    Affiliations
    Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, CONICET, Buenos Aires, Argentina
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  • Author Footnotes
    1 These authors have contributed equally to this work.
    Lilien Chertkoff
    Footnotes
    1 These authors have contributed equally to this work.
    Affiliations
    Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires, Argentina
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  • Author Footnotes
    1 These authors have contributed equally to this work.
    Andrea Mangano
    Footnotes
    1 These authors have contributed equally to this work.
    Affiliations
    Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, CONICET, Buenos Aires, Argentina
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  • Author Footnotes
    1 These authors have contributed equally to this work.
    Claudio Castaños
    Correspondence
    Corresponding author.
    Footnotes
    1 These authors have contributed equally to this work.
    Affiliations
    Servicio de Neumonología, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires, Argentina
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  • Author Footnotes
    1 These authors have contributed equally to this work.
Open ArchivePublished:August 29, 2014DOI:https://doi.org/10.1016/j.jcf.2014.07.012

      Abstract

      Background

      There is a considerable variation in the phenotype and course of the disease in cystic fibrosis (CF) even in patients with the same CFTR genotype, suggesting that other factors are important for prognosis. Mannose-binding lectin (MBL) has been proposed as one of these factors. We therefore investigated the influence of MBL2 gene variants on disease severity, age at acquisition of Pseudomonas aeruginosa, and survival in CF patients.

      Methods

      MBL2 variants were studied in 106 Argentinean pediatric CF patients carrying two severe CFTR mutations. Clinical phenotype was defined according to the Shwachman score and lung function tests. Age at infection with P. aeruginosa and age at death were also recorded.

      Results

      MBL insufficiency was associated with a 3.5-fold risk of having a severe phenotype (CI 95%: 1.2–10.3, p = 0.03). It was also associated with an earlier onset of infection with P. aeruginosa ( p = 0.035). No statistically significant differences were found in FEV 1 and survival.

      Conclusions

      MBL insufficiency was associated with detrimental progression of the disease. These results together with previous findings suggest that the effect of MBL2 expression may be a major determinant of the severity of the clinical phenotype in patients with CF.

      Keywords

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