Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Högenauer, C; Santa Ana, CA; Porter, JL; Millard, M; Gelfand, A; Rosenblatt, RL; Prestidge, CB; Fordtran, JS.
Active intestinal chloride secretion in human carriers of cystic fibrosis mutations: an evaluation of the hypothesis that heterozygotes have subnormal active intestinal chloride secretion.
Am J Hum Genet. 2000; 67(6):1422-1427
Doi: 10.1086/316911
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- Führende Autor*innen der Med Uni Graz
- Hoegenauer Christoph
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- Abstract:
- To explain the very high frequency of cystic fibrosis (CF) mutations in most populations of European descent, it has been proposed that CF heterozygotes have a survival advantage when infected with Vibrio cholerae or Escherichia coli, the toxins of which induce diarrhea by stimulation of active intestinal chloride secretion. Two assumptions underlie this hypothesis: (1) chloride conductance by the CF transmembrane conductance regulator (CFTR) is the rate-limiting step for active intestinal chloride secretion at all levels of expression, from approximately zero in patients with CF to normal levels in people who are not carriers of a mutation; and (2) heterozygotes have smaller amounts of functional intestinal CFTR than do people who are not carriers, and heterozygotes therefore secrete less chloride when exposed to secretagogues. The authors used an intestinal perfusion technique to measure in vivo basal and prostaglandin-stimulated jejunal chloride secretion in normal subjects, CF heterozygotes, and patients with CF. Patients with CF had essentially no active chloride secretion in the basal state, and secretion was not stimulated by a prostaglandin analogue. However, CF heterozygotes secreted chloride at the same rate as did people without a CF mutation. If heterozygotes are assumed to have less-than-normal intestinal CFTR function, these results mean that CFTR expression is not rate limiting for active chloride secretion in heterozygotes. The results do not support the theory that the very high frequency of CF mutations is due to a survival advantage that is conferred on heterozygotes who contract diarrheal illnesses mediated by intestinal hypersecretion of chloride.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Age Factors -
- Chlorides - metabolism
- Continental Population Groups - genetics
- Cystic Fibrosis - genetics
- Cystic Fibrosis Transmembrane Conductance Regulator - genetics
- DNA Mutational Analysis - genetics
- Demography - genetics
- Female - genetics
- Heterozygote - genetics
- Humans - genetics
- Intestines - drug effects
- Male - drug effects
- Middle Aged - drug effects
- Models, Genetic - drug effects
- Molecular Sequence Data - drug effects
- Mutation - genetics
- Prostaglandins - pharmacology
- Sex Factors - pharmacology
- Sodium - metabolism
- Water - metabolism
- Water-Electrolyte Balance - drug effects