Title : The rs2294008 PSCA polymorphism was associated with peptic ulcer disease in men and was not disease-associated in women
Abstract:
In this work, the features of associations of candidate genes polymorphic variants with the formation of peptic ulcer disease (PUD) in men and women living in the Central Chernozem region of Russia are analyzed. The sample consisted of 305 men (188 – patients, 117 – control) and 441 women (211 – patients, 230 – control). For the study, 9 polymorphic loci of candidate genes for PUD of two groups were specially selected: 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). The assessment of the regulatory potential of the studied polymorphic variants was carried out using the online databases 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: It was revealed that in men, the allele T rs2294008 PSCA reduces the risk of developing peptic ulcer disease (additive model: OR=0.64, pperm=0.010; dominant model: OR=0.39; pperm=0.001). Associations with PUD were not revealed in the group of women. The rs2294008 polymorphism of the PSCA gene is located in the areas of hypersensitivity to DNAse and in the regions of histone proteins marking promoters; 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. Conclusion. Polymorphisms rs2294008 PSCA is associated with PUD in men.
