Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-57500
Steiner, B; Rosendahl, J; Witt, H; Teich, N; Keim, V; Schulz, H U; Pfützer, R; Lühr, M; Gress, T M; Nickel, R; Landt, O; Koudova, M; Macek, M; Farre, A; Casals, T; Desax, M C; Gallati, S; Gomez-Lira, M; Audrezet, M P; Férec, C; des Georges, M; Claustres, M; Truninger, K (2011). Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Human Mutation, 32(8):912-920.
PDF - Registered users only
View at publisher
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.
1 download since deposited on 02 Mar 2012
0 downloads since 12 months
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Medical Genetics|
|Dewey Decimal Classification:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||02 Mar 2012 12:28|
|Last Modified:||05 Apr 2016 15:31|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page