To determine whether the CLCA gene family of calcium-activated chloride channels is a modulator of the basic defect of cystic fibrosis (CF), an association study was performed with polymorphic microsatellite markers covering a 40-Mbp region spanning the CLCA gene locus on human chromosome 1p in CF patients displaying CF transmembrane conductance regulator (CFTR)-independent residual chloride conductance in gastrointestinal epithelia. Statistically significant association of the electrophysiological phenotype with the allele distribution of markers 5′ of and within the CLCA locus was observed. Transmission disequilibrium and the significance of the association decreased within the locus from hCLCA2 towards hCLCA4. Expression of hCLCA1 and hCLCA4 in human rectal mucosa was proven by microarray analysis. The CLCA gene region was identified to encode mediators of DIDS-sensitive anion conductance in the human gastrointestinal tract that modulate the CF basic defect.

CaCC, CF, CLCA, DIDS-sensitive Cl- conductance, Human chromosome 1p
dx.doi.org/10.1007/s00439-004-1190-y, hdl.handle.net/1765/62488
Human Genetics
Department of Clinical Genetics

Ritzka, M, Stanke, F, Jansen, S, Gruber, A.D, Pusch, L, Woelfl, S, … Tümmler, B. (2004). The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis. Human Genetics, 115(6), 483–491. doi:10.1007/s00439-004-1190-y