Associations of polymorphic variants of candidate genes with the development of H. pylori-negative duodenal ulcer in residents of the Central Chernozem region of Russia
Background: Peptic ulcer disease (PUD) is a chronic recurrent disease that occurs with alternating periods of exacerbation and remission, the leading manifestation of which is the formation of a defect (ulcer) in the wall of the stomach and duodenum. Hereditary predisposition is one of the etiopathogenetic factors of the development of PUD, therefore, it is necessary to study the genetic determinants of the disease. The aim of the study: To study the role of 9 polymorphic variants of candidate genes for H. pylori-negative duodenal ulcer (DU) specially selected for the study (GWAS-significant for PUD: rs2294008 PSCA, rs505922 ABO; genes of cell adhesion molecules pathogenetically significant for the development of H. pylori-negative DU: rs6136 SELP; rs8176720, rs2519093, rs507666 ABO; rs651007, rs579459, rs649129 ABO/RF00019) in the development of H. pylori-the negative DU in residents of the Central Chernozem region of Russia. Materials and methods: Sample size: 78 patients with H. pylori-negative DU, 347 persons of the control group. The regulatory potential of the loci selected for the study was evaluated using the Internet resources HaploReg v4.1, PolyPhen-2 and GTEx Portal. The analysis of associations was carried out by the method of logistic regression (allelic, additive, dominant and recessive genetic models). Results: Allele C of the SELP gene (rs6136) (allele model: OR=1.88; 95%CI 1.13-3.13; Pperm=0.024; additive model: OR=1.77; 95%CI 1.06-2.96; Pperm=0.023; dominant model: OR=1.93; 95%CI 1.06-3.53; Pperm=0.043) and allele C of the PSCA gene (rs2294008) (recessive model: OR=2.34; 95%CI 1.34-4.08; Pperm=0.003) are associated with an increased risk of H. pylori-negative DU. The polymorphic variant rs6136 SELP and 1 proxy (r2≥0.8) SNP with it affect the expression of the F5 gene and alternative splicing of the BLZF1 gene. The rs2294008 PSCA polymorphism and 48 proxy (r2≥0.8) loci with it have an effect on the expression of 11 genes (ARC, CTD-2292P10.4, JRK, LY6D, LY6K, LYNX1, LYPD2, PSCA, RP11-706C16.7, SLURP1, THEM6) and alternative splicing of 4 genes (JRK, LY6D, LYNX1, THEM6). These genes play a role in key etiopathogenetic processes in peptic ulcer disease: cell growth and division, posttranslational modification of glycosylphosphatidylinositol-anchored proteins, cell adhesion, immune system reactions, activity of nicotine acetylcholine receptors, hemostasis. Conclusion: Allele C of the SELP gene (rs6136) and C of the PSCA gene(rs2294008) are associated with an increased risk of developing H. pylori-negative DU.
Rashina OV. Associations of polymorphic variants of candidate genes with the development of H. pylori-negative duodenal ulcer in residents of the Central Chernozem region of Russia. Research Results in Biomedicine. 2023;9(3):333-346. Russian. DOI: 10.18413/2658-6533-2023-9-3-0-4
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