PRSS1, SPINK1, CFTR, and CTRC Pathogenic Variants in Korean Patients With Idiopathic Pancreatitis

This study aimed to identify pathogenic variants of PRSS1, SPINK1, CFTR, and CTRC genes in Korean patients with idiopathic pancreatitis.

The study population consisted of 116 Korean subjects (65 males, 51 females; mean age, 30.4 yr, range, 1-88 yr) diagnosed with idiopathic chronic pancreatitis (ICP), idiopathic recurrent acute pancreatitis (IRAP), or idiopathic acute pancreatitis (IAP). We analyzed sequences of targeted regions in the PRSS1, SPINK1, CFTR, and CTRC genes, copy numbers of PRSS1 and SPINK1, and clinical data from medical records.

We identified three types of pathogenic PRSS1 variants in 11 patients, including p.N29I (n=1), p.R122H (n=1), and p.G208A (n=9). Sixteen patients exhibited heterozygous pathogenic variants of SPINK1, including c.194+2T>C (n=12), p.N34S (n=3), and a novel pathogenic splicing variation c.194+1G>A. A heterozygous CFTR p.Q1352H pathogenic variant was detected in eight patients. One patient carried a heterozygous CTRC p.P249L pathogenic variant, which is a known high-risk variant for pancreatitis. All patients had normal PRSS1 and SPINK1 gene copy numbers. Weight loss occurred more frequently in patients carrying the p.G208A pathogenic variant, while pancreatic duct stones occurred more frequently in patients with the c.194+2T>C pathogenic variant.

Pathogenic variants of PRSS1, SPINK1, and CFTR were associated with idiopathic pancreatitis, while pathogenic variants of CTRC were not. Copy number variations of PRSS1 and SPINK1 were not detected.