The aim of the studywas to define the spectrum of genetic risk factors of chronic pancreatitis (CP) development in patients living in the European part of the Russian Federation.Materials and MethodsThe study group included 105 patients with CP, with the age of the disease onset under 40 years old (the average age of onset was 26.9 years). The control group consisted of 76 persons without clinical signs of pancreatitis. The diagnosis of chronic pancreatitis in patients was made on the basis of clinical manifestations and the results of laboratory and instrumental investigations. Genetic examination of patients was conducted using the next-generation sequencing (NGS) technology and included targeted sequencing of all exons and exon-intron boundaries of thePRSS1,SPINK1,CTRC,CFTR, andCPA1genes. The genotyping of the rs61734659 locus of thePRSS2gene was also conducted.ResultsGenetic risk factors of the CP development were found in 61% of patients. Pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the following genes:CTRC(37.1% of patients),CFTR(18.1%),SPINK1(8.6%),PRSS1(8.6%), andCPA1(6.7%). The frequent gene variants in Russian patients with CP were as follows:CTRCgene — c.180C>T (rs497078), c.760C>T (rs121909293), c.738_761del24 (rs746224507); cumulative odds ratio (OR) for all risk alleles was 1.848 (95% CI: 1.054–3.243);CFTRgene — c.3485G>T (rs1800120), c.1521_1523delCTT (p.Phe508del, rs113993960), and c.650A>G (rs121909046); OR=2.432 (95% CI: 1.066–5.553). In theSPINK1,PRSS1, andCPA1genes, pathogenic variants were found only in the group of patients with CP. The frequent variants of theSPINK1gene include c.101A>G (p.Asn34Ser, rs17107315) and c.194+2T>C (rs148954387); of thePRSS1gene — c.86A>T (p.Asn29Ile, rs111033566); of theCPA1gene — c.586-30C>T (rs782335525) and c.696+23_696+24delGG. The OR for the CP development for the c.180TT genotype (rs497078)CTRCaccording to the recessive model (TT vs. CT+CC) was 7.05 (95% CI: 0.86–263, p=0.011). In theCTRCgene, the variant c.493+49G>C (rs6679763) appeared to be benign, the c.493+51C>A (rs10803384) variant was frequently detected among both the diseased and healthy persons and did not demonstrate a protective effect. The protective factor c.571G>A (p.Gly191Arg, rs61734659) of thePRSS2gene was detected only in the group of healthy individuals and confirmed its protective role. 12.4% of the patients with CP had risk factors in 2 or 3 genes.ConclusionSequencing of the coding regions of thePRSS1,SPINK1,CTRC,CFTR, andCPA1genes allowed to identify genetic risk factors of the CP development in 61% of cases. Determining the genetic cause of CP helps to predict the disease course, perform preventive measures in the proband’s relatives, and facilitate a personalized treatment of the patient in future.