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

Steiner, Bernhard and Rosendahl, Jonas and Witt, Heiko and Teich, Niels and Keim, Volker and Schulz, Hans-Ulrich and Pfützer, Roland and Löhr, Matthias and Lühr, Matthias and Gress, Thomas M. and Nickel, Renate and Landt, Olfert and Koudova, Monika and Macek, Milan and Farre, Antoni and Casals, Teresa and Desax, Marie-Claire and Gallati, Sabina and Gomez-Lira, Macarena and Audrezet, Marie Pierre and Férec, Claude and des Georges, Marie and Claustres, Mireille and Truninger, Kaspar. (2011) Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Human mutation, Vol. 32, H. 8. pp. 912-920.

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Official URL: http://edoc.unibas.ch/dok/A6005367

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Gastroenterologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Gastroenterologie
UniBasel Contributors:Truninger, Kaspar Ulrich
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Wiley-Liss
ISSN:1098-1004
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:27 Mar 2014 13:13
Deposited On:27 Mar 2014 13:13

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