Is the SPINK1 variant p.N34S overrepresented in patients with acute pancreatitis?
OBJECTIVE
Serine Protease Inhibitor Kazal type 1 (SPINK1) protects against premature intracellular activation of trypsinogen and development of acute pancreatitis. Our aim was to determine the prevalence of SPINK1 mutations (a) in unselected patients with first-time acute pancreatitis and (b) in the Danish background population (c) in a meta-analysis to combine the results with findings in similar investigations worldwide and (d) to evaluate whether patients with SPINK1 mutations had a more severe clinical course.


METHODS
A total of 75 consecutive patients admitted to a surgical department with first-time acute pancreatitis were prospectively included. In addition, 188 healthy controls were tested for the SPINK1 variants: p.N34S, p.P55S, p.R65Q, p.R67C, and IVS3+2 T>C, in order to calculate the prevalence of SPINK1 mutations in the Danish background population. A meta-analysis was conducted on previous studies on acute pancreatitis and SPINK1 mutations.


RESULTS
Two patients (2.7%) and two controls (1.1%) were heterozygous for the p.N34S variant. The meta-analysis confirmed that the p.N34S variant is overrepresented in patients with acute pancreatitis compared with the background population (OR=3.16, P<0.001). But this analysis did not clarify whether this was only true for patients with first-time acute pancreatitis or recurrent pancreatitis as the present studies do not provide this information, and those who do not have enough patients to reach levels of statistic significance, even if data are pooled.


CONCLUSIONS
The SPINK1 variant p.N34S is overrepresented in patients with acute pancreatitis, but more studies distinguishing between first-time and recurrent acute pancreatitis have to be done to determine whether this is only true for patients with recurrent acute pancreatitis.
Department of Medical Gastroenterology S, Odense University Hospital, University of Southern Denmark, Odense, Sweden. maiken.t.joergensen@regionsyddanmark.dk
Maiken Thyregod
MT
Jøergensen
Klaus
K
Brusgaard
Srdan
S
Novovic
Anders Møller
AM
Andersen
Mark Berner
MB
Hansen
Anne-Marie
AM
Gerdes
Ove Bent Schaffalitzky
OB
de Muckadell
D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010195:Pancreatitis / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D014359:Trypsin Inhibitor, Kazal Pancreatic
D015415:Biomarkers; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D002097:C-Reactive Protein