Novel mutation and polymorphism of PRSS1 gene in the Chinese patients with hereditary pancreatitis and chronic pancreatitis
Liu, Q-cai.; Gao, F.; Ou, Q-shui.; Zhuang, Z-hao.; Lin, S-rong.; Yang, B.; Cheng, Z-jian.
Chinese Medical Journal 121(2): 108-111
2008
ISSN/ISBN: 0366-6999 PMID: 18272034 Document Number: 617109
Background Mutations in the cationic trypsinogen gene (PRSS1) have been detected in patients with hereditary pancreatitis (HP). This study investigated the prevalence of the R122H (c.365G>A), A121T (c.361 G>A) and D162D (c.488 C>T) mutations or polymorphisms in the common, non-hereditary forms of chronic pancreatitis and in an HP family.Methods DNA was prepared from blood samples of 54 patients with chronic pancreatitis (35 alcoholic, 17 idiopathic and 2 hereditary) and 120 normal controls. The PRSS1 genes were amplified by polymerase chain reaction (PCR) and their products were analyzed by sequencing and related clinical data were also collected.Results A new polymorphism (c.488 C>T) of PRSS1 was found in 25 patients with chronic pancreatitis (including one affected member of the HP family) and six members of the normal controls. The C/T genotype was significantly increased in chronic pancreatitis (OR. 16.379, 95%Cl: 5.7522-52.3663), the frequency of c.488 C>T change was in according with the Hardy-Weinberg equilibrium, but it doesn't affect the clinical phenotype. The commonly reported change of R122H (c.365G>A) was not detected in any of the study subjects. c.361 G>A was found in 2 affected members and one unaffected carrier in an HP family. One of the affected members of an HP family had c.361 G>A mutation and polymorphism (c.488 C>T) in the PRSS1 gene at the same time. The patient's clinical values (C3, C4, CA19-9 and HbA1c) were higher than those of the other patients with chronic pancreatitis. The two patients with HP developed diabetes mellitus and their father died with pancreatic cancer.Conclusion A new polymorphism (c.488 C>T) in the PRSS1 gene is associated with chronic pancreatitis, but it did not affect the clinical phenotype while the A121T (c.361 G>A) mutation in the gene shows a significant correlation in the patients with HP.