Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the serine protease inhibitor, Kazal type 1 (SPINK1) gene in patients with alcoholic chronic pancreatitis

Abstract

Susceptibility to alcoholic chronic pancreatitis (ACP) could be genetically determined. Mutations in cationic trypsinogen (PRSS1), cystic fibrosis transmembrane conductance regulator (CFTR), and serine protease inhibitor, Kazal type 1 (SPINK1) genes have been variably associated with both the hereditary and the idiopathic form of chronic pancreatitis (CP). Our aim was to analyze the three genes in ACP patients. Mutational screening was performed in 45 unrelated ACP patients and 34 patients with alcoholic liver disease (ALD). No mutation of PRSS1 was found in ACP and ALD patients. Three mutations of CFTR were detected in four ACP patients with a prevalence (8.9%) not significantly different from that observed (3.0%) in ALD patients and from that expected (3.2%) in our geographical area. Neither compound heterozygotes for CFTR nor trans-heterozygotes for CFTR/SPINK1 were found. One ACP patient (2.2%) was found to carry the most common mutation (N34S) of SPINK1 compared to none of the ALD patients (P ¼ NS). In five other patients (two with ACP and three with ALD) other rare variants, including P55S, were found. In contrast with the hereditary and the idiopathic forms of CP, in which mutations of PRSS1, CFTR, and SPINK1 genes may occur, ACP is still a 'gene(s)-orphan' disease. The supposed genetic susceptibility to ACP relies on other yet unknown gene(s) which could affect the alcohol metabolism or modulate the pancreatic inflammatory response to alcohol abuse.

Genetic Mutations in a Spanish Population with Chronic Pancreatitis

“…Several large studies focused on the association of ICP, and the most common trypsinogen mutations (R122H and N29I) have shown a frequency of mutations ranging from 0.2 to 10% of patients [28][29][30][31][32] . PRSS1 mutations are rarely found in ACP patients [33][34][35] . O'Reilly et al [11] described the R122H muta- Age is expressed as median and range.…”

CFTR Polymorphisms in Patients with Alcoholic Chronic Pancreatitis

“…However, the researches have not found any mutations of the PRSS1 gene in patients with alcoholic pancreatitis [8,14] . In Brazil, the E79K change in exon 3 was detected in 1 patient with alcohol-related chronic pancreatitis but with no difference when compared to control subjects [12] .…”

Mutation analysis of PRSS1, SPINK1 and CFTR gene in patients with alcoholic and idiopathic chronic pancreatitis: A single center study

“…This mutation's analysis has always been negative in ACP (13)(14)(15)(16), confirming that PRSS1 mutations play no role in pancreatic damage in patients who drink alcohol. A recent study also showed that PRSS1 mutations were not detected in Indian patients with hereditary and nonhereditary CP, including ACP (17).…”

“…Sharer et al looked for 22 different mutations; in patients with ACP, the CFTR mutation rate was 8.5%; significantly higher than the control group (26). However, subsequent studies failed to establish any significant difference between ACP patients, the healthy population and the control groups (13,14,25,27). Two studies from Brazil showed that different methods could affect the results of the study.…”