Spectrum of PRSS1, SPINK1, CTRC, CFTR, and CPA1 Gene Variants in Chronic Pancreatitis Patients in Russia.

The aim of the study was 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 Methods: The 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 the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes. The genotyping of the rs61734659 locus of the PRSS2 gene was also conducted. Results: Genetic 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%), and CPA1 (6.7%). The frequent gene variants in Russian patients with CP were as follows: CTRC gene - 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); CFTR gene - 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 the SPINK1, PRSS1, and CPA1 genes, pathogenic variants were found only in the group of patients with CP. The frequent variants of the SPINK1 gene include c.101A>G (p.Asn34Ser, rs17107315) and c.194+2T>C (rs148954387); of the PRSS1 gene - c.86A>T (p.Asn29Ile, rs111033566); of the CPA1 gene - c.586-30C>T (rs782335525) and c.696+23_696+24delGG. The OR for the CP development for the c.180TT genotype (rs497078) CTRC according to the recessive model (TT vs. CT+CC) was 7.05 (95% CI: 0.86-263, p=0.011). In the CTRC gene, 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 the PRSS2 gene 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. Conclusion: Sequencing of the coding regions of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes 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.

[Deliberate medication poisoning in adolescence as a medical and socially significant problem].

One of the urgent medical and social problems of modern society is the steady growth of auto-aggressive behavior and deliberate medication poisoning among adolescents and young adults. This investigation was held to optimize the provision of specialized medical care for acute deliberate self-poisoning in teenagers. We examined 498 patients admitted to the Toxicology Department of N. F. Filatov Children City Clinical Hospital No. 13 with a diagnosis of acute deliberate medication poisoning. The diagnosis was confirmed by chemical and toxicological urine test using thin-layer chromatography. From 2016 to 2018 the number of patients with deliberate medication poisoning increased by more than 2.5 times and amounted to 236 cases. Female patients were prevalent and accounted for up to 85% of cases. The leading position among medication self-poisoning is held by psychopharmacological drugs at 56%, in second place are non-steroidal anti-inflammatory drugs at 18.5%. The main causes of self-poisoning were social or family conflicts (47%), problems at school (35%), and Internet-related complaints (18%). The clinical manifestations of the disease in the acute period of chemical poisoning depended on the toxic agent and the dose taken. Psychological testing revealed a high level of neuroticism in 71% of adolescents, severe anxiety was observed in 57% of patients, and depression was diagnosed in 28% of cases. All patients were provided specialized medical care, including resuscitation, detoxification, and psychiatrist examination. Based on the accumulated clinical experience, an algorithm for managing adolescents with deliberate medication poisoning has been developed, which has reduced the number of repeated suicides by 1.8 times.