Original Paper
Pancreatology 2005;5:354–360
DOI: 10.1159/000086535
Mutations in the Serine Protease
Inhibitor Kazal Type 1 (SPINK1) Gene in
Japanese Patients with Pancreatitis
Kiyoshi Kume
a
Atsushi Masamune
a
Hiroya Mizutamari
a
Kenzo Kaneko
a
Kazuhiro Kikuta
a
Masahiro Satoh
a
Kennichi Satoh
a
Kenji Kimura
a
Noriaki Suzuki
a
Yutaka Nagasaki
a
Akira Horii
b
Tooru Shimosegawa
a
a
Division of Gastroenterology, and
b
Department of Molecular Pathology, Tohoku University Graduate School of
Medicine, Sendai, Japan
higher in patients with familial pancreatitis (38 and 13%,
respectively) and with idiopathic CP (13 and 16%) than
normal subjects (0.6 and 0%). In addition, the frequency
of [N34S; IVS1–37T 1 C] mutation was higher in patients
with autoimmune CP (33%). Conclusion: The SPINK1
gene mutations were associated with pancreatitis also
in Japan.
Copyright © 2005 S. Karger AG, Basel and IAP
Introduction
Chronic pancreatitis (CP) is a progressive inflamma-
tory disease that eventually leads to impairment of exo-
crine and endocrine functions of the organ [1, 2]. The
causes of CP are multifaceted. Most causes of CP have
been attributed to alcohol abuse, in some cases hereditary
or metabolic factors play a role, and the actual cause re-
mains unknown in a substantial portion of the patients
[1, 2]. Recent genetic studies have revealed an association
between CP and mutations in the cationic trypsinogen
(protease, serine, 1; PRSS1 ) gene [3–6], the serine prote-
ase inhibitor Kazal type 1 ( SPINK1 , also called pancre-
atic secretory trypsin inhibitor; PSTI ) gene [7–12], and
the cystic fibrosis transmembrane conductance regulator
gene [13, 14] . These genetic findings in CP supported the
Key Words
Pancreatitis Serine protease inhibitor Kazal type 1
Pancreatic secretory trypsin inhibitor Mutational
analysis Familial pancreatitis Autoimmune
pancreatitis
Abstract
Background/Aims: Recent studies have shown an asso-
ciation between the N34S mutation in the serine prote-
ase inhibitor Kazal type 1 (SPINK1) gene and chronic pan-
creatitis (CP). We here examined the prevalence of
SPINK1 mutations in Japanese patients with pancreati-
tis. Methods: Genomic DNA was prepared from 80 Jap-
anese patients with CP, 36 patients with acute pancreati-
tis (AP), and 165 healthy controls. All exons and the
promotor region of the SPINK1 gene were amplified by
the polymerase chain reaction, and directly sequenced.
Results: We found four types of mutation (N34S, IVS1–
37T 1 C, –215G 1 A, and IVS3 + 2T 1 C) and two types of
polymorphism (–253T 1 C and 272C 1 T). The N34S muta-
tion cosegregated with IVS1–37T 1 C, and was present in
8 CP and 1 AP patients. The –215G 1 A mutation was in a
complete linkage with IVS3 + 2T 1 C, and was present in
8 CP and 1 AP patients. The prevalences of [N34S; IVS1–
37T 1 C] and [–215G 1 A; IVS3 + 2T 1 C] were significantly
Received: October 6, 2003
Accepted after revision: May 11, 2004
Published online: June 23, 2005
Tooru Shimosegawa, MD, Division of Gastroenterology
Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho
Aoba-ku, Sendai 980-8574 (Japan)
Tel. +81 22 717 7171, Fax +81 22 717 7177
E-Mail tshimosegawa@int3.med.tohoku.ac.jp
© 2005 S. Karger AG, Basel and IAP
1424–3903/05/0055–0354$22.00/0
Accessible online at:
www.karger.com/pan
Fax +41 61 306 12 34
E-Mail karger@karger.ch
www.karger.com