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Article Dans Une Revue Human Mutation Année : 2011

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

Jonas Rosendahl
Heiko Witt
Niels Teich
  • Fonction : Auteur
Volker Keim
  • Fonction : Auteur
Hans-Ulrich Schulz
  • Fonction : Auteur
Roland Pfützer
  • Fonction : Auteur
Matthias Lühr
  • Fonction : Auteur
Thomas Gress
  • Fonction : Auteur
  • PersonId : 904878
Renate Nickel
  • Fonction : Auteur
Olfert Landt
  • Fonction : Auteur
Monika Koudova
  • Fonction : Auteur
Antoni Farre
  • Fonction : Auteur
Teresa Casals
  • Fonction : Auteur
Marie-Claire Desax
  • Fonction : Auteur
Macarena Gomez-Lira
  • Fonction : Auteur
Marie Pierre Audrezet
  • Fonction : Auteur
Kaspar Truninger
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-02446217 , version 1 (20-01-2020)

Identifiants

Citer

Bernhard Steiner, Jonas Rosendahl, Heiko Witt, Niels Teich, Volker Keim, et al.. Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Human Mutation, 2011, 32 (8), pp.912-920. ⟨10.1002/humu.21511⟩. ⟨hal-02446217⟩
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