Gastric and duodenal peptic ulcer disease is a multifactorial pathology, in the etiopathogenesis of which the general and local reactions of the body to external and internal risk factors play a role. Psychoemotional stress is the main cause of the pathology of nervous and humoral regulation (general reaction), and the local reaction is expressed in a violation of the ratio between the factors of aggression and protection factors in the mucous membrane of the stomach and / or duodenum. The combined action of these components leads to the formation of an ulcerative defect.

With gastric and duodenal peptic ulcer disease, a chronic inflammatory process develops, in which cell adhesion molecules are actively involved. Currently, as a result of genome-wide association studies (GWAS), more than 20 polymorphic variants involved in determining their level have been identified, including rs505922 of the ABO gene. At the same time, this polymorphic variant, according to GWAS, is associated with an increased risk of developing peptic ulcer disease (PUD). It should also be noted that the association of the O(I) blood group according to the ABO system with an increased risk of developing PUD has long been known. Therefore, the genetic determinants of cell adhesion molecules are of interest for studying as candidate genes for peptic ulcer disease.

Hereditary predisposition is one of the aetiopathogenetic factors in the development of gastric ulcer and duodenal ulcer. The analysis of literature materials allows us to identify a number of candidate genes that play a role in the formation of peptic ulcer: PSCA, ABO, IL1β, IL1RN, TNFα, HSP70-1, GSR, TLR4, TLR2, TLR9, MMP-1, MMP-3, MMP- 9, TIMP-3, PGC, MIF, MPO, COX-1. Considering that most of the studies were carried out abroad, the results differ depending on the ethnic characteristics of the studied groups, sometimes they are contradictory, and the works of domestic scientists on this problem are rare, further study of the role of polymorphic variants of candidate genes in the formation of gastric ulcer and duodenal ulcer is necessary.

Introduction. Peptic ulcer of the stomach and duodenum is a chronic recurrent multifactorial disease, the ethiopathogenesis of which is significantly contributed by hereditary predisposition. With this disease, a chronic inflammatory process develops, in which cell adhesion molecules take part. The incidence of peptic ulcer disease (PUD) depends on gender: men get sick 2-7 times more often than women. There are few works on the analysis of gender-specific features of associations of polymorphic loci of candidate genes of YB, therefore, further study of this issue is necessary.Aim: To study the role of two groups of candidate genes of PUD specially selected for the study of 9 polymorphic loci (SNPs): the first – GWAS-significant for peptic ulcer disease (rs2294008 PSCA, rs505922 ABO), the second - genes of cell adhesion molecules pathogenetically significant for the development of PUD (rs6136 SELP; rs8176720, rs2519093, rs507666 ABO; rs651007, rs579459, rs649129 ABO/RF00019), - in the formation of peptic ulcer disease in men and women of the Central Chernozem region of Russia. The sample consisted of 305 men (188 patients, 117 controls) and 441 women (211 patients, 230 controls).Methods. The regulatory potential of SNPs was assessed using Internet resources (HaploReg v4.1, PolyPhen-2, GTEx Portal), the analysis of associations was carried out by the method of logistic regression in the framework of allelic, additive, dominant and recessive genetic models.Results. The allele T rs2294008 of the PSCA gene in the group of men is a protective factor in the development of peptic ulcer disease (OR = 0.39-0.64). This pattern was not revealed in women. The rs2294008 polymorphism of the PSCA gene is located in the regions of histone proteins marking promoters and enhancers in the gastric and esophageal mucosa, in the area of hypersensitivity to DNAse in the stomach, binding sites with the POL2 regulatory protein and the CTCF regulatory motif; it affects the expression of 10 genes, including 4 (LY6K, LYNX1, PSCA, THEM6) in the target organ (stomach), alternative splicing of 3 genes, including 2 genes (JRK, LYNX1) in the tissues of the stomach and esophagus.

Introduction: Peptic ulcer disease occurs in 5-10% of the adult population, and is characterized by a high percentage of complications, which is a serious medical and social problem. The contribution of hereditary factors to the etiopathogenesis of the disease leaves 5.5-50%. The aim of the study was to study the contribution of intergenic interactions of polymorphic variants of candidate genes (rs2294008, rs505922, rs6136, rs8176720, rs2519093, rs507666, rs651007, rs579459, rs649129) to the development of gastric ulcer (GU). Materials and methods: The sample consisted of 217 patients with GU and 347 individuals from the control group, the regulatory potential of polymorphic loci were evaluated using the online databases, and genotyping was performed by PCR. The study of SNP×SNP interactions of polymorphic variants of candidate genes associated with the development of GU was carried out using a modification of the MDR (Multifactor Dimensionality Reduction) - Model-Based-MDR (MB-MDR) method, data visualization was carried out in the form of a dendrogram and graph using MDR software (v. 3.0.2). Results: All 9 studied SNPs as part of 10 significant models of interlocus interactions are involved in the formation of GU. The largest number of models includes rs8176720 of the ABO gene and rs2294008 of the PSCA gene. These polymorphic variants have a pronounced regulatory potential in many organs (tissues), incl. in the target organ of GU (stomach).