SPINK1 N34S is strongly associated with recurrent acute pancreatitis but is not a risk factor for the first or sentinel acute pancreatitis event.
OBJECTIVE
Serine protease inhibitor Kazal type 1 (SPINK1) gene mutations have been associated with chronic pancreatitis of different etiologies; however, little is known about their role in the pathogenesis of acute pancreatitis (AP). Our aim was to study the prevalence of the SPINK1 N34S polymorphism in patients with sentinel and recurrent AP (RAP).


METHODS
Patients with AP were enrolled, and genetic tests were carried out to detect the SPINK1 N34S polymorphism. Subjects without pancreatitis from the North American Pancreatitis Study were used as controls.


RESULTS
A total of 188 patients (116 with sentinel AP and 72 with recurrent attacks) and 670 controls were evaluated. The SPINK1 N34S polymorphism was detected in 1 of 232 alleles in patients with sentinel AP, 11 of 144 alleles in patients with RAP, and in 19 of 1,340 control alleles. There was no difference in the prevalence of the polymorphism between sentinel attack patients and controls. Patients with the polymorphism were more prone to develop recurrent attacks (odds ratio (OR)=19.1, 95% confidence interval (CI): 2.4-149.6).


CONCLUSIONS
The SPINK1 N34S polymorphism was not associated with the sentinel AP attack, but it substantially increases the risk of recurrent attacks. Additional studies are needed to further elucidate the mechanism of SPINK1-associated protection in AP.
Aoun
Elie
E
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Muddana
Venkata
V
Papachristou
Georgios I
GI
Whitcomb
David C
DC
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010195:Pancreatitis / Q000235:genetics*; D011110:Polymorphism, Genetic; D012008:Recurrence; D012307:Risk Factors; D014359:Trypsin Inhibitor, Kazal Pancreatic
D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic