Association of the CLCA1 p.S357N variant with meconium ileus in European patients with cystic fibrosis.
In Cftr-/- mice that mostly die because of intestinal obstruction, intestinal expression of Clca3 is decreased, whereas upregulation of Clca3 results in amelioration of intestinal disease. The aim of the study was to investigate whether the p.S357N variant in CLCA1, the human orthologue of Clca3, acts as a modifier gene in a cohort of 682 European patients with cystic fibrosis (CF)-99 patients with meconium ileus. The 357SS genotype was significantly overrepresented in both patients with meconium ileus and also with a severe CFTR genotype (P = 0.009) and in p.F508del homozygotes (P = 0.002). This suggests that CLCA1 has similar important functions in CF-related intestinal obstruction in humans as in Cftr-/- mice.
van der Doef
H P J
HP
Department of Pediatric Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands. h.p.j.vanderdoef@umcutrecht.nl
Slieker
M G
MG
Staab
D
D
Alizadeh
B Z
BZ
Seia
M
M
Colombo
C
C
van der Ent
C K
CK
Nickel
R
R
Witt
H
H
Houwen
R H J
RH
D000293:Adolescent; D000328:Adult; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005060:Europe; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D045823:Ileus / Q000150:complications / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D008470:Meconium; D055815:Young Adult
C492109:CLCA1 protein, human; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator