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The role of SNP×SNP interactions of polymorphic loci of candidate genes in the pathogenesis of duodenal ulcer

https://doi.org/10.31146/1682-8658-ecg-224-4-37-42

Abstract

Introduction: Duodenal ulcer is the most common disease of the gastrointestinal tract with a prevalence of 4-15%, occurs 4 times more often in prevalence with peptic ulcer and occurs more often from 30 to 55 years. The contribution of hereditary factors to the etiopathogenesis of diseases is 5.5-50%. Objective: to evaluate the role of SNP×SNP interactions of polymorphic loci of candidate genes (rs2294008, rs505922, rs6136, rs8176720, rs2519093, rs507666, rs651007, rs579459, rs649129) in the development of duodenal ulcer (DU). Materials and methods: The sample consisted of 217 patients with DU and 347 individuals of the control group, the regulatory potential of polymorphic loci was evaluated using the online databases, 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: Six out of 9 studied SNPs as part of 5 significant models of interlocus interactions are involved in the formation of duodenal ulcer. The largest number of models includes rs2294008 of the PSCA gene, rs8176720 and rs579459 of the ABO gene. These polymorphic variants have a pronounced regulatory potential in many organs (tissues), incl. in the organs of the digestive system.

About the Authors

O. V. Rashina
Belgorod State National Research University
Russian Federation


I. N. Sorokina
Belgorod State National Research University
Russian Federation


V. S. Orlova
Belgorod State National Research University
Russian Federation


O. A. Efremova
Belgorod State National Research University
Russian Federation


I. V. Batlutskaya
Belgorod State National Research University
Russian Federation


M. I. Churnosov
Belgorod State National Research University
Russian Federation


I. V. Ponomarenko
Belgorod State National Research University
Russian Federation


References

1. Ivashkin V. T., Maev I. V., Tsar’kov P.V. et al. Diagnosis and Treatment of Peptic Ulcer in Adults (Clinical Guidelines of the Russian Gastroenterological Association, Russian Society of Colorectal Surgeons and the Russian Endoscopic Society).Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(1):49-70. (In Russ.) doi: 10.22416/1382-4376-2020-30-1-49-70.@@ Ивашкин В. Т., Маев И. В., Царьков П. В. и соавт. Диагностика и лечение язвенной болезни у взрослых (Клинические рекомендации Российской гастроэнтерологической ассоциации, Российского общества колоректальных хирургов и Российского эндоскопического общества). Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2020;30(1):49-70. doi: 10.22416/1382-4376-2020-30-1-49-70.

2. Minyaylo O. N., Ponomarenko I. V., Churnosov M. I. Gender-Specific Features of Associations of Polymorphism of Matrix Metalloproteinase Genes with the Development of Peptic Ulcer Disease in the Population of the Central Chernozem Region of Russia. Genetics. 2021;57(10):1185-1193. (In Russ.) doi: 10.31857/S0016675821100088.@@ Миняйло О. Н., Пономаренко И. В., Чурносов М. И. Гендерные особенности ассоциаций полиморфизма генов матриксных металлопротеиназ с развитием язвенной болезни у населения Центрального Черноземья России. Генетика. 2021;57(10):1185-1193. (In Russ.) doi: 10.31857/S0016675821100088.

3. Minyaylo O. N. Allele distribution and haploblock structure of matrix metalloproteinase gene polymorphism in patients with H. pylori-negative gastric ulcer and duodenal ulcer. Research Results in Biomedicine. 2020;6(4):488-502. (in Russ.) doi: 10.18413/2658-6533-2020-6-4-0-5.@@ Миняйло О. H. Распределение аллелей и гаплоблочная структура полиморфизма генов матриксных металлопротеиназ у больных Н. pylori-негативной язвенной болезнью желудка и двенадцатиперстной кишки. Научные результаты биомедицинских исследований. 2020;6(4):488-502. doi: 10.18413/2658-6533-2020-6-4-0-5.

4. Minyaylo O., Ponomarenko I., Reshetnikov E., Dvornyk V., Churnosov M. Polymorphisms of the matrix metalloproteinase 9 gene are associated with duodenal ulcer in a Caucasian population of Central Russia. Journal of King Saud University - Science. 2022;34(6):102142.

5. Dvornyk V., Ponomarenko I., Minyaylo O., Reshetnikov E., Churnosov M. Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia. PLoS One. 2021 Sep 7;16(9): e0257060. doi: 10.1371/journal.pone.0257060.

6. Minyaylo O., Ponomarenko I., Reshetnikov E., Dvornyk V., Churnosov M. Functionally significant polymorphisms of the MMP-9 gene are associated with peptic ulcer disease in the Caucasian population of Central Russia. Sci Rep. 2021 Jun 29;11(1):13515. doi: 10.1038/s41598-021-92527-y.

7. Rashina O. V. 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. (in Russ.) doi: 10.18413/2658-6533-2023-9-3-0-4.@@ Рашина О. В. Ассоциации полиморфных вариантов генов-кандидатов с развитием H. pylori-негативной язвенной болезни двенадцатиперстной кишки у жителей Центрального Черноземья России. Научные результаты биомедицинских исследований. 2023;9(3):333-346. doi: 10.18413/2658-6533-2023-9-3-0-4.

8. Rashina O. V., Churnosov M. I. Peptic ulcer candidate genes. Experimental and Clinical Gastroenterology. 2021;186(2): 52-57. (In Russ.) doi: 10.31146/1682-8658-ecg-186-2-52-57.@@ Рашина О. В., Чурносов М. И. Гены-кандидаты язвенной болезни. Экспериментальная и клиническая гастроэнтерология. 2021;186(2): 52-57. doi: 10.31146/1682-8658-ecg-186-2-52-57.

9. Rashina O.V., Churnosov M. I. Multi-Factor etiopathogenesis of gastric and duodenal peptic ulcer disease. Experimental and Clinical Gastroenterology. 2021;192(8): 154-159. (In Russ.) doi: 10.31146/1682-8658-ecg-192-8-154-159.@@ Рашина О. В., Чурносов М. И. Многофакторный этиопатогенез язвенной болезни желудка и двенадцатиперстной кишки. Экспериментальная и клиническая гастроэнтерология. 2021;192(8): 154-159. doi: 10.31146/1682-8658-ecg-192-8-154-159.

10. Tanikawa C., Urabe Y., Matsuo K., Kubo M., Takahashi A., Ito H., Tajima K., Kamatani N., Nakamura Y., Matsuda K. A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population. Nat Genet. 2012 Mar 4;44(4):430-4, S1-2. doi: 10.1038/ng.1109.

11. Wu Y., Murray G. K., Byrne E. M., Sidorenko J., Visscher P. M., Wray N. R. GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression. Nature Communications. 2021;12:1146. doi: 10.1038/s41467-021-21280-7.

12. García-González M.A., Bujanda L., Quintero E., Santolaria S. et al. Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease.International Journal of Cancer. 2015;137(6):1362-1373. doi: 10.1002/ijc.29500.

13. Usui Y., Matsuo K., Oze I., Ugai T. et al. Impact of PSCA polymorphism on the risk of duodenal ulcer. Journal of epidemiology. 2021;31(1):12-20. doi: 10.2188/jea.JE20190184.

14. Tanikawa C., Matsuo K., Kubo M. et al. Impact of PSCA variation on gastric ulcer susceptibility. PLoS One. 2013;8(5). doi: 10.1371/journal.pone.0063698.

15. Galustian C., Elviss N., Chart H., Owen R., Feizi T.Interactions of the gastrotropic bacterium Helicobacter pylori with the leukocyte-endothelium adhesion molecules, the selectins - a preliminary report. FEMS Immunology and Medical Microbiology. 2003, no36. pp.127-134. doi: 10.1016/S0928-8244(03)00021-X.

16. Rashina O. V., Churnosov M. I. The role of cell adhesion molecules in the inflammatory process and development of gastric and duodenal peptic ulcer disease, their molecular genetic determinants. Experimental and Clinical Gastroenterology. 2022;(9):201-208. (In Russ.) doi: 10.31146/1682-8658-ecg-205-9-201-208.@@ Рашина О. В., Чурносов М. И. Роль молекул клеточной адгезии в воспалительном процессе и развитии язвенной болезни желудка и двенадцатиперстной кишки, их молекулярно- генетические детерминанты. Экспериментальная и клиническая гастроэнтерология. 2022;(9):201-208. doi: 10.31146/1682-8658-ecg-205-9-201-208.

17. Ponomarenko IV. Using the method of Multifactor Dimensionality Reduction (MDR) and its modifications for analysis of gene-gene and gene-environment interactions in genetic-epidemiological studies (review). Research Results in Biomedicine. 2019;5(1):4-21. (in Russ.) doi: 10.18413/2313-8955-2019-5-1-0-1.@@ Пономаренко И. В. Использование метода Multifactor Dimensionality Reduction (MDR) и его модификаций для анализа ген-генных и генно-средовых взаимодействий при генетико-эпидемиологических исследованиях (обзор). Научные результаты биомедицинских исследований. 2019;5(1):4-21. doi: 10.18413/2313-8955-2019-5-1-0-1.

18. GeneCards: The Human Gene Database: Available at: https://www.genecards.org. Accessed: 22.07.2022.

19. OMIM: An Online Catalog of Human Genes and Genetic Disorders: Available at: https://www.omim.org. Accessed: 22.07.2022.

20. Oguma J., Ozawa S., Sakakibara T., Kajiwara H., Nakamura N., Makuuchi H. Prognostic impact of LY6K and CDCA1 expression for patients with esophageal squamous cell carcinoma. Ann Gastroenterol Surg. 2020;14;5(2):194-203. doi: 10.1002/ags3.12415.

21. Suhre K., Arnold M., Bhagwat A. M. et al. Connecting genetic risk to disease endpoints through the human blood plasma proteome. Nat Commun. 2017, no8. doi: 10.1038/ncomms14357.

22. Paterson A. D., Lopes-Virella M.F., Waggott D., Boright A. P., Hosseini S. M., Carter R. E., Shen E., Mirea L., Bharaj B., Sun L., Bull S. B.; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin. Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1958-67. doi: 10.1161/ATVBAHA.109.192971.

23. Barbalic M., Dupuis J., Dehghan A. et al. Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels. Hum Mol Genet. 2010 May 1;19(9):1863-72. doi: 10.1093/hmg/ddq061.

24. Emilsson V., Ilkov M., Lamb J. R. et al. Co-regulatory networks of human serum proteins link genetics to disease. Science. 2018 Aug 24;361(6404):769-773. doi: 10.1126/science.aaq1327.


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For citations:


Rashina O.V., Sorokina I.N., Orlova V.S., Efremova O.A., Batlutskaya I.V., Churnosov M.I., Ponomarenko I.V. The role of SNP×SNP interactions of polymorphic loci of candidate genes in the pathogenesis of duodenal ulcer. Experimental and Clinical Gastroenterology. 2024;(4):37-42. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-224-4-37-42

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