CLCA4 variants determine the manifestation of the cystic fibrosis basic defect in the intestine

The manifestation of the monogenic disease cystic fibrosis results from the cystic fibrosis transmembrane conductance regulator (CFTR)-mediated basic defect defined as an altered chloride transport. An association study using contrasting endophenotypes was conducted with 17 markers to allow fine-map...

Full description

Saved in:
Bibliographic Details
Published inEuropean journal of human genetics : EJHG Vol. 21; no. 6; pp. 691 - 694
Main Authors Kolbe, Ernst-Wolfgang, Tamm, Stephanie, Hedtfeld, Silke, Becker, Tim, Tümmler, Burkhard, Stanke, Frauke
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.06.2013
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:The manifestation of the monogenic disease cystic fibrosis results from the cystic fibrosis transmembrane conductance regulator (CFTR)-mediated basic defect defined as an altered chloride transport. An association study using contrasting endophenotypes was conducted with 17 markers to allow fine-mapping of a previously reported association signal within the CLCA gene cluster. Markers were analyzed for association with the manifestation of the basic defect in the patient population of the European CF Twin and Sibling Study composed of 101 families with a total of 171 patients. The manifestation of the basic defect was associated with markers rs11807298-rs6684219, encompassing the CLCA4 promoter (Praw=0.0013; Pcorr=0.0157). Refined analysis of the CLCA4 association signal among F508del homozygous CF patients who exhibit either no, CFTR-mediated or Ca(2+)-mediated residual chloride conductance revealed that allele distributions for markers rs11807298-rs113894048-rs6684219 differed significantly among these three patient groups. Our data strongly argue that CLCA4 modulates the capability to express residual chloride secretion in colonic tissue. The latter finding is in consistency with the now favored role of the CLCA proteins in signal transduction in epithelial cells.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Article-2
ObjectType-Feature-1
ISSN:1018-4813
1476-5438
DOI:10.1038/ejhg.2012.234