Ancestral haplotype 8.1 and lung disease severity in European cystic fibrosis patients

Harriet Corvol, Julie Beucher, Pierre-Yves Boelle, Pierre-Francois Busson, Celine Muselet-Charlier, Annick Clement, Felix Ratjen, Hartmut Grasemann, Judith Laki, Colin N. A. Palmer, J. Stuart Elborn, Anil Mehta

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    22 Citations (Scopus)


    Background: The clinical course of cystic fibrosis (CF) lung disease varies between patients bearing identical CFTR mutations. This suggests that additional genetic modifiers may contribute to the pulmonary phenotype. The highly conserved ancestral haplotype 8.1 (8.1AH), carried by up to one quarter of Caucasians, comprises linked gene polymorphisms on chromosome 6 that play a key role in the inflammatory response: LTA +252A/G; TNF -308G/A, HSP70-2 +1267A/G and RAGE -429T/C. As inflammation is a key component inducing CF lung damage, we investigated whether the 8.1AH represents a lung function modifier in CF.

    Methods: We analyzed the lung function of 404 European CF patients from France (n=230), Germany (n=95) and UK (n=79). FEV1 differences between 8.1AH carriers and non-carriers were calculated in each country and pooled using a random effects model.

    Results: The frequency of 8.1AH carriers was similar between French (22%), German (29%) and UK (27%) patients. We found that 8.1AH carriers had significantly lower FEVI, adjusted for age classes and countries (P<0.04, mean FEV1 difference -6.4% CI95% [-12.4%, -0.5%]). No difference was observed with respect to BMI Z-scores and chronic colonization with P. aeruginosa.

    Conclusions: These findings support the concept that 8.1AH is an important genetic modifier of lung disease in CF. To conclude, multiple linked genes outside the CF locus might explain some of the variability in lung phenotype. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)63-67
    Number of pages5
    JournalJournal of Cystic Fibrosis
    Issue number1
    Publication statusPublished - Jan 2012


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