Genetic Variability in the CPA1 Gene and Its Impact on Acute Pancreatitis Risk: New Insights from a Large-Scale Study

Acute pancreatitis (AP) is a common and potentially lethal disease. Over the last 10 years, AP has become one of the most important healthcare problems. On a global scale, the incidence has increased by 63% over the last 20 years. AP is usually caused by gallstones and excessive alcohol consumption and genetic factors play an important role in the development of inflammation. Recent studies involving the CPA1 mutations are ambiguous and dependent on the population studied. In this study, the variability of the CPA1 gene in patients with AP was analyzed. Genetic material was isolated from the blood of 301 patients with AP and 184 healthy individuals. Identification of the variants in exons 5, 6, 8, and 9 with introns was performed using molecular biology methods. Mutations were identified by comparison to the reference sequence (NM_001868.4). Statistical analysis included the identification of mutations correlating with the risk of AP, the etiology of inflammation, and family history. Several novel mutations in the CPA1 gene have been identified, along with a high degree of variability within the coding region of the carboxypeptidase gene. A correlation between mutations CPA1:c.1072 + 84del; c.987 + 57G>A and increased risk of developing AP was found. Two protective mutations, CPA1:c.625A>T, c.1072 + 94del, were identified. The CPA1 gene is characterized by high sequence variability and regions in which mutations lead to an increased risk of developing AP. Single or co-occurring mutations of the CPA1 gene can significantly affect the risk of developing AP.