Alimentary TractResidual chloride secretion in intestinal tissue of ΔF508 homozygous twins and siblings with cystic fibrosis☆,☆☆
Section snippets
Subjects
Twin and sibling pairs with CF with different genotypes were enrolled for the European Cystic Fibrosis Twin and Sibling Study. For the study described here, only subjects homozygous for the CFTR gene mutation ΔF508 were selected. We invited 72 patients belonging to dizygous twin or sibling pairs and 26 patients belonging to monozygous twin pairs. Patients were investigated in or near their home countries at selected CF core centers in Hannover, Innsbruck, London, Rotterdam, and Verona.
Chloride-secretory response in CF intestine
Of the participating patients belonging to a sibling or dizygous twin pair, 49 responses to 8-bromo-cAMP + forskolin, 56 to carbachol, and 41 to histamine could be determined. Eighteen 8-bromo-cAMP + forskolin, 20 carbachol, and 14 histamine responses from participating patients of monozygous twin pairs were collected. The mean basal transepithelial resistance of the rectal biopsy specimens of our group of ΔF508 homozygous CF patients was 27 Ω·cm2. The mean basal Isc was 20 μA/cm2.
Patients for
Discussion
This study investigated the presence and frequency of chloride-secretory responses in the rectal tissue of ΔF508 homozygous CF twins and siblings upon stimulation with cAMP- and Ca2+-linked agonists, before and after incubation of the tissue with DIDS. Forty (73%) of the ΔF508 homozygotes expressed a cAMP-stimulated chloride-secretory response in their intestinal tissue. Because cAMP-regulated chloride conductance is indicative of CFTR,2, 3, 27 this finding suggests the presence of some active
Acknowledgements
The authors thank the collaborating patients, parents, physicians and scientists for their cooperation, particularly H. Ellemunter (Innsbruck), G. Mastella (Verona), S. Thomas (London), J. Versloot, H. Otten, and R. Samlal-Soedhoe (The Netherlands).
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Address requests for reprints to: Inez Bronsveld, Laboratory of Pediatrics, rm Ee-1500, Erasmus University Rotterdam, P.O. Box 1738, 3000 Rotterdam, The Netherlands. e-mail: [email protected]; fax: (31) 20-8706751.
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This work was executed as part of the European Cystic Fibrosis Twin and Sibling Study and supported by the BIOMED II program of the EU, the Deutsche Forschungsgemeinschaft, the Deutsche Fördergesellschaft für die Mukoviszidoseforschung eV, and the Mukoviszidose eV.