Is the SPINK1 variant p.N34S overrepresented in patients with acute pancreatitis?

TY - JOUR

T1 - Is the SPINK1 variant p.N34S overrepresented in patients with acute pancreatitis?

AU - Jøergensen, Maiken Thyregod

AU - Brusgaard, Klaus

AU - Novovic, Srdan

AU - Andersen, Anders Møller

AU - Hansen, Mark Berner

AU - Gerdes, Anne-Marie

AU - de Muckadell, Ove Bent Schaffalitzky

N1 - Author(s): Joergensen, MT (Joergensen, Maiken Thyregod)[ 1 ] ; Brusgaard, K (Brusgaard, Klaus)[ 2 ] ; Novovic, S (Novovic, Srdan)[ 4 ] ; Andersen, AM (Andersen, Anders Moller)[ 4 ] ; Hansen, MB (Hansen, Mark Berner)[ 4,5 ] ; Gerdes, AM (Gerdes, Anne-Marie)[ 2,3 ] ; de Muckadell, OBS (de Muckadell, Ove Bent Schaffalitzky)[ 1 ] 1 ] Univ So Denmark, Dept Med Gastroenterol S, Odense Univ Hosp, DK-5000 Odense C, Denmark [ 2 ] Univ So Denmark, Dept Clin Genet, Odense Univ Hosp, DK-5000 Odense C, Denmark [ 3 ] Univ Copenhagen, Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark [ 4 ] Univ Copenhagen, Bispebjerg Hosp, Dept Surg K, Copenhagen, Denmark [ 5 ] AstraZeneca Res & Dev, Molndal, Sweden

PY - 2012/3

Y1 - 2012/3

N2 - Objectives: 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. Conclusion: 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.

AB - Objectives: 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. Conclusion: 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.

U2 - 10.1097/meg.0b013e32834ee5e2

DO - 10.1097/meg.0b013e32834ee5e2

M3 - Journal article

C2 - 22228370

SN - 0954-691X

VL - 24

SP - 309

EP - 315

JO - European Journal of Gastroenterology and Hepatology, Supplement

JF - European Journal of Gastroenterology and Hepatology, Supplement

IS - 3

ER -