Gender-specific features of associations of polymorphic loci of candidate genes with the formation of peptic ulcer in the population of the Central Chernozem Region of Russia

Abstract

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.Conclusions. The T allele of rs2294008 of the PSCA gene in the group of men is a protective factor in the development of ulcer disease. Polymorphism rs2294008 of the PSCA gene affects the expression of ten genes in the target organ (stomach), alternative splicing of three genes, including two genes in the stomach and esophagus tissues.