Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens

Publisher DOI
PubMed ID
21520337
Abstract
CFTR mutations enhance susceptibility for idiopathic chronic pancreatitis (ICP) and congenital bilateral absence of the vas deferens (CBAVD); however, it is unknown why CFTR heterozygotes are at increased disease risk. We recently showed that common CFTR variants are associated with aberrantly spliced transcripts. Here, we genotyped for common CFTR variants and tested for associations in two ICP (ICP-A: 126 patients, 319 controls; ICP-B: 666 patients, 1,181 controls) and a CBAVD population (305 patients, 319 controls). Haplotype H10 (TG11-T7-470V) conferred protection (ICP-A: OR 0.19, P<0.0001; ICP-B: OR 0.78, P = 0.06; CBAVD OR 0.08, P<0.001), whereas haplotype H3 (TG10-T7-470M) increased disease risk (ICP-A: OR 8.34, P = 0.003; ICP-B: OR 1.88, P = 0.007; CBAVD: OR 5.67, P = 0.01). The risk of heterozygous CFTR mutations carriers for ICP (OR 2.44, P<0.001) and CBAVD (OR 14.73, P<0.001) was fully abrogated by the H10/H10 genotype. Similarly, ICP risk of heterozygous p.Asn34Ser SPINK1 mutation carriers (OR 10.34, P<0.001) was compensated by H10/H10. Thus, common CFTR haplotypes modulate ICP and CBAVD susceptibility alone and in heterozygous CFTR and p.Asn34Ser mutation carriers. Determination of these haplotypes helps to stratify carriers into high- and low-risk subjects, providing helpful information for genetic counseling.
Date Issued
2011
Publication Type
Article
Language(s)
en
Author(s)
Steiner, Bernhard
Rosendahl, Jonas
Witt, Heiko
Teich, Niels
Keim, Volker
Schulz, Hans-Ulrich
Pfützer, Roland
Löhr, Matthias
Lühr, Matthias
Gress, Thomas M
Nickel, Renate
Landt, Olfert
Koudova, Monika
Macek, Milan
Farre, Antoni
Casals, Teresa
Desax, Marie-Claire
Gomez-Lira, Macarena
Audrezet, Marie Pierre
Férec, Claude
des Georges, Marie
Claustres, Mireille
Truninger, Kaspar
Additional Credits
Journal
Human mutation
Publisher
Wiley-Blackwell
ISSN
1059-7794
Access(Rights)
metadata.only
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