Genetic mutations in SPINK1, CFTR, CTRC genes in acute pancreatitis

BMC Gastroenterol. 2015 Jun 23;15:70. doi: 10.1186/s12876-015-0302-6.


Background: Explanation of the ultimate causes of acute and chronic pancreatitis is challenging. Hence, it is necessary to seek various etiological factors, including genetic mutations that may be of importance in triggering recurrence and progression of acute to chronic pancreatitis. The aim of this study was to determine the frequency of genetic mutations in patients with acute pancreatitis and to investigate their relationship with the etiology and clinical course.

Methods: The study included 221 patients treated for acute pancreatitis and 345 healthy subjects as a control group. Peripheral blood samples were collected from each study participant and genomic DNA was isolated. Genotyping of common mutations in the SPINK1 (p.N34S and p.P55S) and CTRC (p.I259V, p.V235I, p.K247_R254del, p.E225A) genes was performed using the high-resolution melting method. Mutations in the CFTR p.F508del (delF508_CTT) were genotyped using allele-specific amplification polymerase chain reaction. All detected mutations were confirmed with direct capillary DNA sequencing.

Results: Mutations in SPINK 1, CFTR and CTRC were detected in 6.3%, 2.3% and 1.8% of patients with acute pancreatitis versus 3.2%, 3.8% and 1.2% of volunteers in the control group. No relationship was found between the detected mutations and severity of acute pancreatitis: mild acute pancreatitis, mutation of CFTR in 4 (2.8%) and CTRC in 2 (1.4%) patients; severe acute pancreatitis, mutation of CFTR and CTRC in 1 (2.6%) case each. The SPINK1 mutation was significantly more frequent in 8 (10.4%) severe cases than in 6 (4.2%) mild cases (P < 0.05), and was observed in 5/70 (7.1%) patients with alcohol-related AP, 5/81 (6.2%) with biliary AP, and 4/63 (6.3%) in those without any established cause of the disease.

Conclusions: Mutation p.N34S in SPINK1 may predispose patients to acute pancreatitis, especially in those abusing alcohol, and may promote a more severe course of the disease.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Chymotrypsin / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Disease Progression
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genotype
  • Genotyping Techniques
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pancreatitis / genetics*
  • Pancreatitis, Chronic / genetics
  • Trypsin Inhibitor, Kazal Pancreatic


  • CFTR protein, human
  • Carrier Proteins
  • Genetic Markers
  • SPINK1 protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Trypsin Inhibitor, Kazal Pancreatic
  • Chymotrypsin
  • chymotrypsin C