Hirtz, Stephanie and Gonska, Tanja and Seydewitz, Hans H. and Thomas, Jörg and Greiner, Peter and Kuehr, Joachim and Brandis, Matthias and Eichler, Irmgard and Rocha, Herculano and Lopes, Ana-Isabel and Barreto, Celeste and Ramalho, Anabela and Amaral, Margarida D. and Kunzelmann, Karl and Mall, Marcus (2004) CFTR Cl- channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis. GASTROENTEROLOGY, 127 (4). pp. 1085-1095. ISSN 0016-5085, 1528-0012
Full text not available from this repository. (Request a copy)Abstract
Background &Aims: Cystic fibrosis (CF) is caused by over 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and presents with a widely variable phenotype. Genotype-phenotype studies identified CFTR mutations that were associated with pancreatic sufficiency (PS). Residual Cl- channel function was shown for selected PS mutations in heterologous cells. However, the functional consequences of most CFTR mutations in native epithelia are not well established. Methods: To elucidate the relationships between epithelial CFTR function, CFTR genotype, and patient phenotype, we measured cyclic adenosine monophosphate (cAMP)-mediated Cl- secretion in rectal biopsy specimens from 45 CF patients who had at least 1 nonDeltaF508 mutation carrying a wide spectrum of CFTR mutations. We compared CFTR genotypes and clinical manifestations of CF patients who expressed residual CFTR-mediated Cl- secretion with patients in whom Cl- secretion was absent. Results: Residual anion secretion was detected in 40% of CF patients, and was associated with later disease onset (P < 0.0001), higher frequency of PS (P < 0.000:1), and less severe lung disease (P < 0.05). Clinical outcomes correlated with the magnitude of residual CFTR activity, which was in the range of similar to12%-54% of controls. Conclusions: Specific CFTR mutations confer residual CFTR function to rectal epithelia, which is related closely to a mild disease phenotype. Quantification of rectal CFTR-mediated Cl- secretion may be a sensitive test to predict the prognosis of CF disease and identify CF patients who would benefit from therapeutic strategies that would increase residual CFTR activity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSMEMBRANE CONDUCTANCE REGULATOR; DISEASE-ASSOCIATED MUTATIONS; DEPENDENT HCO3-TRANSPORT; AIRWAY ION-TRANSPORT; CHLORIDE CHANNEL; PULMONARY-DISEASE; MESSENGER-RNA; LUNG-DISEASE; PANCREATIC-FUNCTION; RECTAL BIOPSIES; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jun 2021 08:15 |
| Last Modified: | 28 Jun 2021 08:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37113 |
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