Host genetic polymorphisms as risk factors for H. pylori-positive peptic ulcer

Rashina O.V.; Churnosov M.I.

doi:https://doi.org/10.17116/dokgastro20231201114

Close metadata

OBJECTIVE

To study the role of genetic variants of candidate genes (rs2294008 of the PSCA gene, rs6136 of the SELP gene, rs505922, rs8176720, rs2519093, rs507666 of the ABO gene, rs651007, rs579459, and rs649129 of the ABO/RF00019 gene) in the development of H.pylori-positive PUD.

MATERIALS AND METHODS

In the current study, there were 347 individuals in the control group and 98 patients with H.pylori-positive PUD. The assessment of the regulatory potential of the SNPs selected for study was carried out using the Internet resources HaploReg v. 4.1, PolyPhen-2, and GTEx Portal, and genotyping was carried out by the polymerase chain reaction (PCR). The logistic regression method was used for association analysis (allelic, additive, dominant, and recessive genetic models).

RESULTS

The C allele of the SELP gene (rs6136) is a genetic risk factor for the development of H. pylori-positive PUD (OR=1.66; 95% CI=1.02—2.71; p=0.041; p_perm=0.042). The rs6136 polymorphism is non-synonymous and has a strong regulatory potential. The rs6136 allele C, which raises the chance of developing H.pylori-positive PUD, is linked to increased F5 gene expression and decreased BLZF1 gene alternative splicing.

CONCLUSIONS

The C allele of the SELP gene (rs6136) is a genetic risk factor for the development of H.pylori-positive PUD.

Keywords:

Single nucleotide polymorphism

Helicobacter pylori

peptic ulcer

risk factors

genotype

Authors:

Rashina O.V.

Belgorod National Research University

Churnosov M.I.

Belgorod State National Research University

ORCID: 0000-0003-1254-6134

Received:

02.10.2022

Accepted:

18.01.2023

Close metadata

References:

Ivashkin VT, Maev IV, Tsar’kov PV, Korolev MP, Andreev DN, Baranskaya EK, Burkov SG, Derinov AA, Efetov SK, Lapina TL, Pavlov PV, Pirogov SS, Tkachev AA, Trukhmanov AS, Fedorov ED, Sheptulin AA. Diagnosis and Treatment of Peptic Ulcer in Adults (Clinical Guidelines of the Russian Gastroenterological Association, the Russian Society of Colorectal Surgeons and the Russian Endoscopic Society). Rossijskij zhurnal gastroenterologii, gepatologii, koloproktologii. 2020;30(1):49-70. (In Russ.). https://doi.org/10.22416/1382-4376-2020-30-1-49-70
Ramakrishnan K, Salinas RC. Peptic Ulcer Disease. American Family Physician. 2007;76(7):1005-1012.
Feldmal M, Friedman LS, Brandt J, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Philadelphia: Saunders Elsevier; 2015.
Lanas A, Chan FKL. Peptic ulcer disease. Lancet. 2017;390(10094): 613-624. https://doi.org/10.1016/S0140-6736(16)32404-7
McQuaid KR. Peptic ulcer disease. In: Papadakis MA, McPhee SJ, Rabow MW, eds. Current Medical Diagnosis and Treatment 2020. 59th ed. New York: McGraw-Hill Education; 2020.
Kuna L, Jakab J, Smolic R, Raguz-Lucic N, Vcev A, Smolic M. Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. Journal of Clinical Medicine. 2019;8(2):179. https://doi.org/10.3390/jcm8020179
Dhar P, Nq GZ, Sutton P. How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2016;311(3):514-520. https://doi.org/10.1152/ajpgi.00146.2016
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;36(3):127-134. https://doi.org/10.1016/S0928-8244(03)00021-X
Rashina OV, Churnosov MI. Multi- Factor etiopathogenesis of gastric and duodenal peptic ulcer disease. Eksperimental’naya i klinicheskaya gastroenterologiya. 2021;(8):154-159. (In Russ.). https://doi.org/10.31146/1682-8658-ecg-192-8-154-159
Kuramshina OA, Kryukova AYa. Clinical and endoscopic characteristics and emotional and personal sphere of patients with duodenal ulcer with hereditary predisposition. Fundamental’nye issledovaniya. 2011;11:53-56. (In Russ.).
Paré G, Chasman DI, Kellogg M, Zee RY, Rifai N, Badola S, Miletich JP, Ridker PM. Novel Association of ABO Histo-Blood Group Antigen with Soluble ICAM-1: Results of a Genome-Wide Association Study of 6578 Women. PloS Genetics. 2008;4(7):e1000118. https://doi.org/10.1371/journal.pgen.1000118
Paré G, Ridker PM, Rose L, Barbalic M, Dupuis J, Dehghan A, Bis JC, Benjamin EJ, Shiffman D, Parker AN, Chasman DI. Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci. PloS Genetics. 2011;7(4):e1001374. https://doi.org/10.1371/journal.pgen.1001374
Paterson AD, Lopes-Virella MF, Waggott D, Boright AP, Hosseini SM, Carter RE, Shen E, Mirea L, Bharaj B, Sun L, Bull SB; 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. Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29(11):1958-1967. https://doi.org/10.1161/ATVBAHA.109.192971
Barbalic M, Dupuis J, Dehghan A, Bis JC, Hoogeveen RC, Schnabel RB, Nambi V, Bretler M, Smith NL, Peters A, Lu C, Tracy RP, Aleksic N, Heeriga J, Keaney JF Jr, Rice K, Lip GY, Vasan RS, Glazer NL, Larson MG, Uitterlinden AG, Yamamoto J, Durda P, Haritunians T, Psaty BM, Boerwinkle E, Hofman A, Koenig W, Jenny NS, Witteman JC, Ballantyne C, Benjamin EJ. Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels. Human Molecular Genetics. 2010;19(9):1863-1872. https://doi.org/10.1093/hmg/ddq061
Qi L, Cornelis MC, Kraft P, Jensen M, van Dam RM, Sun Q, Girman CJ, Laurie CC, Mirel DB, Hunter DJ, Rimm E, Hu FB. Genetic variants in ABO blood group region, plasma soluble E-selectin levels and risk of type 2 diabetes. Human Molecular Genetics. 2010;19(9):1856-1862. https://doi.org/10.1093/hmg/ddq057
Enroth S, Johansson A, Enroth SB, Gyllensten U. Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs. Nature Communications. 2014;5:4684. https://doi.org/10.1038/ncomms5684
Suhre K, Arnold M, Bhagwat AM, Cotton RJ, Engelke R, Raffler J, Sarwath H, Thareja G, Wahl A, DeLisle RK, Gold L, Pezer M, Lauc G, El-Din Selim MA, Mook-Kanamori DO, Al-Dous EK, Mohamoud YA, Malek J, Strauch K, Grallert H, Peters A, Kastenmüller G, Gieger C, Graumann J.Connecting genetic risk to disease end points through the human blood plasma proteome. Nature Communications. 2017;8:14357. https://doi.org/10.1038/ncomms14357
Sun BB, Maranville JC, Peters JE, Stacey D, Staley JR, Blackshaw J, Burgess S, Jiang T, Paige E, Surendran P, Oliver-Williams C, Kamat MA, Prins BP, Wilcox SK, Zimmerman ES, Chi A, Bansa N, Spain SL, Wood AM, Morrell NW, Bradley JR, Janjic N, Roberts DJ, Ouwehand WH, Todd JA, Soranzo N, Suhre K, Paul DS, Fox CS, Plenge RM, Danesh J, Runz H, Butterworth AS. Genomic atlas of the human plasma proteome. Nature. 2018;558(7708):73-79. https://doi.org/10.1038/s41586-018-0175-2
Emilsson V, Ilkov M, Lamb JR, Finkel N, Gudmundsson EF, Pitts R, Hoover H, Gudmundsdottir V, Horman SR, Aspelund T, Shu L, Trifonov V, Sigurdsson S, Manolescu A, Zhu J, Olafsson Ö, Jakobsdottir J, Lesley SA, To J, Zhang J, Harris TB, Launer LJ, Zhang B, Eiriksdottir G, Yang X, Orth AP, Jennings LL, Gudnason V. Co-regulatory networks of human serum proteins link genetics to disease. Science. 2018;361(6404):769-773. https://doi.org/10.1126/science.aaq1327
Sliz E, Kalaoja M, Ahola-Olli A, Raitakari O, Perola M, Salomaa V, Lehtimäki T, Karhu T, Viinamäki H, Salmi M, Santalahti K, Jalkanen S, Jokelainen J, Keinänen-Kiukaanniemi S, Männikkö M, Herzig KH, Järvelin MR, Sebert S, Kettunen J. Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns. Journal of Medical Genetics. 2019;56:607-616. https://doi.org/10.1136/jmedgenet-2018-105965
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. Nature Genetics. 2012; 4(44):430-436. https://doi.org/10.1038/ng.1109
Wu Y, Murray GK, Byrne EM, Sidorenko J, Visscher PM, Wray NR. GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression. Nature Communications. 2021;12:1146. https://doi.org/10.1038/s41467-021-21280-7
Tanikawa C, Matsuo K, Kubo M, Takahashi A, Ito H, Tanaka H, Yatabe Y, Yamao K, Kamatani N, Tajima K, Nakamura Y, Matsuda K. Impact of PSCA variation on gastric ulcer susceptibility. PLoS One. 2013;8(5):0063698. https://doi.org/10.1371/journal.pone.0063698
García-González MA, Bujanda L, Quintero E, Santolaria S, Benito R, Strunk M, Sopeña F, Thomson C, Pérez-Aisa A, Nicolás-Pérez D, Hijona E, Carrera-Lasfuentes P, Piazuelo E, Jiménez P, Espinel J, Campo R, Manzano M, Geijo F, Pellise M, Zaballa M, González-Huix F, Espinós J, Titó L, Barranco L, Pazo-Cid R, Lanas A. 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. https://doi.org/10.1002/ijc.29500
Usui Y, Matsuo K, Oze I, Ugai T, Koyanagi Y, Maeda Y, Ito H, Hishida A, Takeuchi K, Tamura T, Tsukamoto M, Kadomatsu Y, Hara M, Nishida Y, Shimoshikiryo I, Takezaki T, Ozaki E, Matsui D, Watanabe I, Suzuki S, Watanabe M, Nakagawa-Senda H, Mikami H, Nakamura Y, Arisawa K, Uemura H, Kuriki K, Takashima N, Kadota A, Ikezaki H, Murata M, Nakatochi M, Momozawa Y, Kubo M, Wakai K. Impact of PSCA polymorphism on the risk of duodenal ulcer. Journal of Epidemiology. 2021;31(1):12-20. https://doi.org/10.2188/jea.JE20190184
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;16(9):e0257060. https://doi.org/10.1371/journal.pone.0257060
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. https://doi.org/10.1016/j.jksus.2022.102142
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. Scientific Reports. 2021;11(1):13515. https://doi.org/10.1038/s41598-021-92527-y
Minyaylo ON, Ponomarenko IV, Churnosov MI. 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. Genetica. 2021;57(10):1185-1193. (In Russ.). https://doi.org/10.31857/S0016675821100088
Minyaylo ON. 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.). https://doi.org/10.18413/2658-6533-2020-6-4-0-5
Rashina OV, Churnosov MI. Peptic ulcer candidate genes. Eksperimental’naya i klinicheskaya gastroenterologiya. 2021;(2):52-57. (In Russ.). https://doi.org/10.31146/1682-8658-ecg-186-2-52-57
Mattar R, Marques SB, Dos Santos AF, do Socorro Monteiro M, Iriya K, Carrilho FJ. A possible role of IL-1RN gene polymorphism in the outcome of gastrointestinal diseases associated with H. pylori infection. Clinical and Experimental Gastroenterology. 2013;6:35-41. https://doi.org/10.2147/CEG.S42260
Essadik A, Jouhadi H, Rhouda T, Nadifiyine S, Kettani A, Maachi F. Polymorphisms of Tumor Necrosis Factor Alpha in Moroccan Patients with Gastric Pathology: New Single-Nucleotide Polymorphisms in TNF-α (-193) (G/A). Mediators of Inflammation. 2015;143941. https://doi.org/10.1155/2015/143941
Pohjanen VM, Koivurova OP, Huhta H, Helminen O, Mäkinen JM, Karhukorpi JM, Joensuu T, Koistinen PO, Valtonen JM, Niemelä SE, Karttunen RA, Karttunen TJ. Toll-Like Receptor 4 Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk. PLoS One. 2015;10(7):e0131553. https://doi.org/10.1371/journal.pone.0131553
Tourani M, Habibzadeh M, Shokri-Shirvani J, Teymournejad O, Mostafazadeh A, Khafri S, Nouri HR. Shokri-Shirvani Association of Helicobacter pylori infection with Toll-like receptor-4 Thr399Ile polymorphism increased the risk of peptic ulcer development in North of Iran. Journal of Pathology, Microbiology and Immunology. 2017;126(1):76-84. https://doi.org/10.1111/apm.12779
Mirkamandar E, Nemati M, Hayatbakhsh MM, Bassagh A, Khosravimashizi A, Jafarzadeh A. Association of a single nucleotide polymorphism in the TLR2 gene (rs3804099), but not in the TLR4 gene (rs4986790), with Helicobacter pylori infection and peptic ulcer. The Turkish Journal of Gastroenterology. 2018;29(3):283-291. https://doi.org/10.5152/tjg.2018.17484
Trejo-de la O A, Torres J, Sánchez-Zauco N, Pérez-Rodríguez M, Camorlinga-Ponce M, Flores-Luna L, Lazcano-Ponce E, Maldonado-Bernal C. Polymorphisms in TLR9 but not in TLR5 increase the risk for duodenal ulcer and alter cytokine expression in the gastric mucosa. Innate Immunity. 2015;21(7):706-713. https://doi.org/10.1177/1753425915587130
GeneCards: The Human Gene Database. Accessed July 22, 2022. https://www.genecards.org
OMIM: An Online Catalog of Human Genes and Genetic Disorders. Accessed July 22, 2022. https://www.omim.org
Litovskij IA, Gordienko AV. Discussion issues of the pathogenesis of gastroduodenal ulcers. Vestnik Rossijskoj voenno-medicinskoj akademii. 2015;4(52):197-204. (In Russ.).