Novel mutation and polymorphism of PRSS1 gene in the Chinese patients with hereditary pancreatitis and chronic pancreatitis

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.