• PMID: 21520337
• Gene Name: CFTR
• Condition: Congenital bilateral absence of the vas deferens (CBAVD), idiopathic obstructive azoospermia
• Association: 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 informatio
• Mutation: p.Asn34Ser
• Population size: 624
• Population details: 624 (305 patients, 319 controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Congenital bilateral absence of the vas deferens (CBAVD), idiopathic obstructive azoospermia

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

Steiner B, Rosendahl J, Witt H, Teich N, Keim V, Schulz HU, Pfützer R, Löhr M, Gress TM, Nickel R, Landt O, Koudova M, Macek M Jr, Farre A, Casals T, Desax MC, Gallati S, Gomez-Lira M, Audrezet MP, Férec C, des Georges M, Claustres M, Truninger K.

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. CI - © 2011 Wiley-Liss, Inc. FAU - Steiner, Bernhard AU - Steiner B AD - Institute of Medical Genetics, University of Zurich, Schwerzenbach and Children's Hospital, Cantonal Hospital Lucerne, Lucerne, Switzerland. FAU - Rosendahl, Jonas AU - Rosendahl J FAU - Witt, Heiko AU - Witt H FAU - Teich, Niels AU - Teich N FAU - Keim, Volker AU - Keim V FAU - Schulz, Hans-Ulrich AU - Schulz HU FAU - Pfützer, Roland AU - Pfützer R FAU - Löhr, Matthias AU - Löhr M FAU - Gress, Thomas M AU - Gress TM FAU - Nickel, Renate AU - Nickel R FAU - Landt, Olfert AU - Landt O FAU - Koudova, Monika AU - Koudova M FAU - Macek, Milan Jr AU - Macek M Jr FAU - Farre, Antoni AU - Farre A FAU - Casals, Teresa AU - Casals T FAU - Desax, Marie-Claire AU - Desax MC FAU - Gallati, Sabina AU - Gallati S FAU - Gomez-Lira, Macarena AU - Gomez-Lira M FAU - Audrezet, Marie Pierre AU - Audrezet MP FAU - Férec, Claude AU - Férec C FAU - des Georges, Marie AU - des Georges M FAU - Claustres, Mireille AU - Claustres M