Affiliations: Department of Legal Medicine, Shinshu University
School of Medicine, Matsumoto, Japan | Department of Medicine, Division of Hepatology and
Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan | Department of Pharmacy, Shinshu University School of
Medicine, Matsumoto, Japan | Center for Health, Safety and Environmental
Management, Shinshu University, Matsumoto, Japan
Abstract: Autoimmune pancreatitis (AIP), characterized by irregular narrowing
of the main pancreatic duct, swelling of the pancreas, and histological
evidence of lymphoplasmacytic inflammation by high serum immunoglobulin G4, is
distinct from ordinary pancreatitis. However, genetic factors involved in the
etiology and pathophysiology of AIP remain unclear. Sixty-four patients with
autoimmune pancreatitis (53 men, 11 women; mean age, 62.4 years) and 104
healthy Japanese controls were enrolled in this study. We performed an
association analysis using 400 microsatellite markers with an average spacing
of 10.8 cM in the genome. We also evaluated the association of AIP with seven
single nucleotide polymorphisms (SNPs) within the 20-kb region around the
potassium voltage-gated channel, shaker-related subfamily, member 3 gene
(KCNA3). We identified six statistically significant markers (D1S2726, D5S410,
D6S460, D10S548, D15S128, and D20S186; P< 0.05) related to susceptibility.
The surrounding region showing the strong association (P=7.4 ×
10^{-7}, Pc=0.0015) contained the KCNA3 gene. Further
analysis by SNP genotyping in KCNA3 gene revealed that four SNPs (rs2840381,
rs1058184, rs2640480, rs1319782) were significantly associated with the AIP
susceptibility (P< 0.007). KCNA3 is known to be involved in immunomodulation
of autoreactive effector and memory T cell--mediated autoimmune diseases. Our
findings provide the first evidence that KCNA3 is associated with AIP and
suggest that KCNA3 may influence the risk for AIP.
