RT Journal Article
SR Electronic
T1 <em>CFTR</em>, <em>SPINK1</em>, <em>CTRC</em> and <em>PRSS1</em> variants in chronic pancreatitis: is the role of mutated <em>CFTR</em> overestimated?
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 582
OP 592
DO 10.1136/gutjnl-2011-300645
VO 62
IS 4
A1 Jonas Rosendahl
A1 Olfert Landt
A1 Jana Bernadova
A1 Peter Kovacs
A1 Niels Teich
A1 Hans Bödeker
A1 Volker Keim
A1 Claudia Ruffert
A1 Joachim Mössner
A1 Andreas Kage
A1 Michael Stumvoll
A1 David Groneberg
A1 Renate Krüger
A1 Werner Luck
A1 Matthias Treiber
A1 Michael Becker
A1 Heiko Witt
YR 2013
UL http://gut.bmj.com/content/62/4/582.abstract
AB Objective In chronic pancreatitis (CP), alterations in several genes have so far been described, but only small cohorts have been extensively investigated for all predisposing genes. Design 660 patients with idiopathic or hereditary CP and up to 1758 controls were enrolled. PRSS1, SPINK1 and CTRC were analysed by DNA sequencing, and cystic fibrosis transmembrane conductance regulator (CFTR) by melting curve analysis. Results Frequencies of CFTR variants p.R75Q, p.I148T, 5T-allele and p.E528E were comparable in patients and controls. We identified 103 CFTR variants, which represents a 2.7-fold risk increase (p&lt;0.0001). Severe cystic fibrosis (CF)-causing variants increased the risk of developing CP 2.9-fold, and mild CF-causing variants 4.5-fold (p&lt;0.0001 for both). Combined CF-causing variants increased CP risk 3.4-fold (p&lt;0.0001), while non-CF-causing variants displayed a 1.5-fold over-representation in patients (p=0.14). CFTR compound heterozygous status with variant classes CF-causing severe and mild represented an OR of 16.1 (p&lt;0.0001). Notably, only 9/660 (1.4%) patients were compound heterozygotes in this category. Trans-heterozygosity increased CP risk, with an OR of 38.7, with 43/660 (6.5%) patients and 3/1667 (0.2%) controls being trans-heterozygous (p&lt;0.0001). Conclusions Accumulation of CFTR variants in CP is less pronounced than reported previously, with ORs between 2.7 and 4.5. Only CF-causing variants reached statistical significance. Compound and trans-heterozygosity is an overt risk factor for the development of CP, but the number of CFTR compound heterozygotes in particular is rather low. In summary, the study demonstrates the complexity of genetic interactions in CP and a minor influence of CFTR alterations in CP development.