The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis.
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.
Ritzka
Margit
M
Department of Pediatrics and Clinical CF Research Group, Medical School Hannover, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
Stanke
Frauke
F
Jansen
Silke
S
Gruber
Achim D
AD
Pusch
Larissa
L
Woelfl
Stefan
S
Veeze
Henk J
HJ
Halley
Dicky J
DJ
Tümmler
Burkhard
B
D000483:Alleles; D000838:Anions; D018118:Chloride Channels / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000235:genetics*; D004200:Diseases in Twins; D004594:Electrophysiology; D005192:Family Health; D041981:Gastrointestinal Tract / Q000473:pathology; D005819:Genetic Markers; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007477:Ions; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D009092:Mucous Membrane / Q000473:pathology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D012313:RNA / Q000737:chemistry
D000838:Anions; C492109:CLCA1 protein, human; C496604:CLCA4 protein, human; D018118:Chloride Channels; D005819:Genetic Markers; D007477:Ions; D012313:RNA