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• W2007070816 abstract "BackgroundThe 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.MethodsWe 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.ResultsThe 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 FEV1, 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.ConclusionsThese 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." @default.
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• W2007070816 date "2012-01-01" @default.
• W2007070816 modified "2023-10-18" @default.
• W2007070816 title "Ancestral haplotype 8.1 and lung disease severity in European cystic fibrosis patients" @default.
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• W2007070816 doi "https://doi.org/10.1016/j.jcf.2011.09.006" @default.
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