The SPINK1 N34S variant is associated with acute pancreatitis.
OBJECTIVE
Acute pancreatitis (AP) is a disease whose pathogenesis remains largely obscure. Genetic research has focussed attention upon the role of the pancreatic protease/protease inhibitor system. The aim of this study was to investigate the prevalence of genetic variants of the trypsin inhibitor, SPINK1, in acute pancreatitis.


METHODS
We genotyped 468 patients with AP and 1117 healthy controls for SPINK1 alterations by single-strand conformation polymorphism analysis and by melting curve analysis using fluorescence resonance energy transfer probes.


RESULTS
The c.101A>G (p.N34S) variant was detected in 24/936 alleles of patients and in 18/2234 alleles of healthy controls (odds ratio=3.240; 95% confidence interval: 1.766-5.945; P<0.001). In the UK patients, the mean age of patients with N34S was 11.9 years younger compared with N34S negative patients (P=0.023), but this was not apparent in the German patients. Allele frequencies for the c.163C>T (p.P55S) variant did not differ between patients and controls.


CONCLUSIONS
The SPINK1 N34S variant is associated with acute pancreatitis. This supports the importance of premature protease activation in the pathogenesis of AP and suggests that mutated SPINK1 may predispose certain individuals to develop this disease.
O'Reilly
Derek A
DA
Department of Surgery, Derriford Hospital, University of Plymouth, Plymouth, UK. doreilly@doctors.org.uk
Witt
Heiko
H
Rahman
Sakhawat H
SH
Schulz
Hans-Ulrich
HU
Sargen
Kevin
K
Kage
Andreas
A
Cartmell
Mark T
MT
Landt
Olfert
O
Larvin
Michael
M
Demaine
Andrew G
AG
McMahon
Michael J
MJ
Becker
Michael
M
Kingsnorth
Andrew N
AN
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D014359:Trypsin Inhibitor, Kazal Pancreatic
D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic