Contribution of intergenic interactions of polymorphic variants of candidate genes to the development of gastric ulcer

Abstract

Introduction: Gastric ulcer is a chronic disease with a recurrent course. The morphological substrate during periods of exacerbation are ulcers of the gastric mucosa. Peptic ulcer disease has a high prevalence among the adult population and is often characterized by a complicated course. Hereditary predisposition, along with other external and internal risk factors, plays a role in the etiopathogenesis of the disease. The aim of the study: To evaluate the effect of polymorphic variants of cell adhesion molecule genes on the development of Helicobacter pylori-negative gastric ulcer (GU). Materials and methods: 119 patients with Helicobacter pylori-negative GU and 347 individuals of the control group were examined. The regulatory potential of 7 polymorphic loci of genes of cell adhesion molecules pathogenetically significant for the development of gastric ulcer (rs6136 of the SELP gene, rs8176720, rs2519093, rs507666 of the ABO gene, rs651007, rs579459, rs649129 of the ABO/RF00019 gene) was evaluated using the HaploReg v4.1, PolyPhen-2, GTEx Portal Internet resources. DNA samples isolated from peripheral blood were genotyped by PCR. 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 T allele of the RF00019/ABO gene (rs651007) is a protective factor in the development of H. pylori-negative GU (OR=0.14). This polymorphism is located in the region of histones marking promoters, regions of hypersensitivity to DNAse and the HNF4 regulatory motif, is associated with the expression of the ABO and SURF1 genes and alternative splicing of the ABO and LCN1P1 genes in various organs (tissues), including in the organs of the digestive and nervous systems.