AGER -429T-C Is Associated with an Increased Lung Disease Severity in Cystic FibrosisReportar como inadecuado

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The clinical course of cystic fibrosis CF varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T-C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T-C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele C was associated with poorer lung function p = 0.03. In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele p = 0.016 in BEAS-2B cells. AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.

Autor: Julie Beucher, Pierre-Yves Boëlle, Pierre-François Busson, Céline Muselet-Charlier, Annick Clement, Harriet Corvol, on behalf



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