A. Persu et al., CF gene and cystic fibrosis transmembrane conductance regulator expressionin autosomal dominant polycystic kidney disease, J AM S NEPH, 11(12), 2000, pp. 2285-2296
Disease-modifying genes might participate in the significant intrafamilial
variability of the renal phenotype in autosomal dominant polycystic kidney
disease (ADPKD). Cys tic fibrosis (CF) transmembrane conductance regulator
(CFTR) is a chloride channel that promotes intracystic fluid secretion, and
thus cyst progression, in ADPKD. The hypothesis that mutations of the CF g
ene, which encodes CFTR, might be associated with a milder renal phenotype
in ADPKD was tested. A series of 117 unrelated ADPKD probands and 136 unaff
ected control subjects were screened for the 1.2 most common mutations and
the frequency of the alleles of the intron 8 polymorphic Tn locus of CF. Th
e prevalence of CF mutations was not significantly different in the ADPKD (
1.7%, n = 2) and control (3.7%, n = 5) groups. The CF mutation was Delta F5
08 in all cases, except for one control subject (1717-1G -->A). The frequen
cies of the 5T, 7T, and 9T intron 8 alleles were also similar in the ADPKD
and control groups. Two additional patients with ADPKD and the Delta F508 m
utation were detected in the families of the two probands with CF mutations
. Kidney volumes and renal function levels were similar for these four pati
ents with ADPKD and Delta F508 CFTR (heterozygous for three and homozygous
for one) and for control patients with ADPKD collected in the University of
Colorado Health Sciences Center database. The absence of a renal protectiv
e effect of the homozygous Delta F508 mutation might be related to the lack
of a renal phenotype in CF and the variable, tissue-specific expression of
Delta F508 CFTR. Immunohistochemical analysis of a kidney from the patient
with ADPKD who was homozygous for the Delta F508 mutation substantiated th
at hypothesis, because CFTR expression was detected in 75% of cysts (compar
ed with <50% in control ADPKD kidneys) and at least partly in the apical me
mbrane area of cyst-lining cells. These data do not exclude a potential pro
tective role of some CFTR mutations in ADPKD but suggest that it might be r
elated to the nature of the mutation and renal expression of the mutated CF
TR.