Affiliations: Department of Internal Medicine, Shinshu University
School of Medicine, Matsumoto, Japan | Center for Health, Safety and Environmental
Management, Shinshu University, Matsumoto, Japan | Department of Pharmacy, Shinshu University School of
Medicine, Matsumoto, Japan | Department of Legal Medicine, Shinshu University
School of Medicine, Matsumoto, Japan
Note: [] Corresponding author: Masao Ota, Ph.D., Department of Legal
Medicine, Shinshu University School of Medicine, 3-1-1 Asahi Matusmoto,
390-8621, Japan. Tel.: +81 263 373 217, Fax: +81 263 373 084; E-mail:
otamasao@shinshu-u.ac.jp
Abstract: Alcohol abuse is one of the most common risk factor for chronic
pancreatitis, but the underlying pathophysiological mechanisms remain unclear.
The aim of this study was to identify genes that contribute to susceptibility
or resistance for alcoholic chronic pancreatitis by screening the whole genome.
Sixty-five patients with alcoholic chronic pancreatitis (63 men and 2 women,
mean age 55.2 years) and 99 healthy Japanese controls were enrolled in this
study. This was an association study using 400 polymorphic microsatellite
markers with an average spacing of 10.8 cM distributed throughout the whole
genome. This search revealed 10 candidate susceptibility regions and 5
candidate resistant regions throughout the genome. No specific microsatellite
markers were detected in association with previously reported susceptibility
genes for chronic pancreatitis, such as PRSS1, PRSS2, CTRC, SPINK1, CFTR,
ALDH2, and CYP2E1. Among the statistically significant markers, D15S1007
on chromosome 15q14 showed strong evidence for disease susceptibility (70.8%
vs. 35.1%, Pc = 0.0001). Within 500 kb of D15S1007, several genes
were candidate genes for susceptibility, including FMN1, DKFZP686C2281,
LOC440268, RYR3, and AVEN, This study identified 10 candidate
susceptibility and 5 candidate resistant regions that may contain genes
involved in ACP pathogenesis.
