1. bookVolume 23 (2015): Issue 2 (June 2015)
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
access type Open Access

AGT A-20C (rs5050) gene polymorphism and ulcer occurrence in patients treated with low-dose aspirin: a case-control study / Polimorfismul AGT A-20C și ulcerele gastro-duodenale la pacienții sub tratament cu aspirină în doze antiagregante: studiu caz-control

Published Online: 23 Jun 2015
Volume & Issue: Volume 23 (2015) - Issue 2 (June 2015)
Page range: 179 - 187
Received: 14 Dec 2014
Accepted: 18 May 2015
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

Genetic factors may play a role in prediction of gastrointestinal side effects of aspirin, one of the most used drugs worldwide. We aim to determine a possible correlation between AGT A-20C (rs5050) gene polymorphism and gastro-duodenal ulcer in patients taking low-dose aspirin, adjusted for clinical and histological characteristics.

Results. We enrolled 211 patients stratified according to AGT A-20C genotype: 122 AA, 83 AC and 6 CC patients. There were no significant differences regarding demographical and clinical parameters, except for the frequency of ulcers (4%, 8.4% respective 50%, p=0.03), endoscopic bleeding signs (12.3%, 14.5% respective 50%, p=0.0001) and the frequency of gastritis in biopsy (63.9%, 54.2% respective 16.7%, p=0.03) in genotype groups. When we compared ulcer and non-ulcer group, variant homozygous CC genotype carried an increased risk for ulcer (OR:9.66, 95% CI: 1.46-63.7, p=0.04) than AA group, as well as variant C allele compared with normal A allele (OR: 2.12, 95% CI: 1.07-4.63, p=0.04). On multivariate analysis, variant homozygous CC genotype AGT A-20C showed an OR: 12.32 (95% CI:1.40 -108.13, p=0.02) for ulcer, while H. pylori infection (OR:2.40, 95% CI:1.18 -6.54, p=0.04) and concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR:1.31, 95% CI:1.07 - 2.27, p=0.05) remained predictors for ulcer in aspirin consumers.

Conclusions. Variant C allele and variant homozygous CC genotype AGT A-20C, infection with H. pylori and NSAIDs co-treatment are risk factors for gastro-duodenal ulcer in low-dose aspirin consumers. The variant homozygous CC genotype AGT A-20C patients treated with LDA are more prone to have reactive gastropathy and bleeding ulcers in a population with a high prevalence of H. pylori infection

Keywords

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1. Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, et al; American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2008;118(18):1894-909. DOI: 10.1161/CIRCULATIONAHA. 108.191087Search in Google Scholar

2. Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther. 2009;29(9):938-46. DOI: 10.1111/j.1365-2036.2009.03960.x10.1111/j.1365-2036.2009.03960.xSearch in Google Scholar

3. Leung Ki EL, Chan FK. Interaction of Helicobacter pylori infection and low-dose aspirin in the upper gastrointestinal tract: implications for clinical practice. Best Pract Res Clin Gastroenterol. 2012;26(2):163-72. DOI: 10.1016/j.bpg.2012.01.00610.1016/j.bpg.2012.01.006Search in Google Scholar

4. Sostres C, Gargallo CJ, Lanas A. Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights. World J Gastroenterol. 2014;20(28):9439-50.Search in Google Scholar

5. Valkhoff VE, Sturkenboom MC, Kuipers EJ. Risk factors for gastrointestinal bleeding associated with low-dose aspirin. Best Pract Res Clin Gastroenterol. 2012;26(2):125-40. DOI: 10.1016/j.bpg.2012.01.01110.1016/j.bpg.2012.01.011Search in Google Scholar

6. Pilotto A, Seripa D, Franceschi M, Scarcelli C, Colaizzo D, Grandone E, et al. Genetic susceptibility to non-steroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology. 2007;133:465-71. DOI: 10.1053/j.gastro.2007.05.02510.1053/j.gastro.2007.05.025Search in Google Scholar

7. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan. Int J Mol Med. 2007;20(3):373-8.Search in Google Scholar

8. Shiotani A, Sakakibara T, Yamanaka Y, Nishi R, Imamura H, Fujita M, et al. The preventive factors for aspirin-induced peptic ulcer: aspirin ulcer and corpus atrophy. J Gastroenterol. 2009;44(7):717-25. DOI: 10.1007/s00535-009-0068-010.1007/s00535-009-0068-0Search in Google Scholar

9. Shiotani A, Nishi R, Yamanaka Y, Murao T, Matsumoto H, Tarumi K, et al. Renin-angiotensin system associated with risk of upper GI mucosal injury induced by low dose aspirin: renin angiotensin system genes’ polymorphism. Dig Dis Sci. 2011;56(2):465-71. DOI: 10.1007/ s10620-010-1382-310.1007/s10620-010-1382-3Search in Google Scholar

10. Garg M, Angus PW, Burrell LM, Herath C, Gibson PR, Lubel JS. Review article: the pathophysiological roles of the renin-angiotensin system in the gastrointestinal tract. Aliment Pharmacol Ther. 2012;35(4):414-28. DOI: 10.1111/j.1365-2036.2011.04971.x10.1111/j.1365-2036.2011.04971.xSearch in Google Scholar

11. Hallersund P, Elfvin A, Helander HF, Fandriks L. The expression of reninangiotensin system components in the human gastric mucosa. J Renin Angiotensin Aldosterone Syst. 2011;12(1):54-64. DOI: 10.1177/147032031037906610.1177/1470320310379066Search in Google Scholar

12. Lanza FL. Endoscopic studies of gastric and duodenal injury after the use of ibuprofen, aspirin and other NSAIDs. Am J Med. 1984;77(1A): 19-24. DOI: 10.1016/S0002-9343(84)80014-510.1016/S0002-9343(84)80014-5Search in Google Scholar

13. Zhang N, Yang L, Cui H, Fu W. Epidemiological Study of AGT Gene Polymorphism among Chinese Subjects with Primary Hypertension. Adv Pharmacoepidem Drug Safety. 2012;1:110. DOI: 10.4172/2167-1052.100011010.4172/2167-1052.1000110Search in Google Scholar

14. Zhao YY, Zhou J, Narayanan CS, Cui Y, Kumar A. Role of C/A polymorphism at -20 on the expression of human angiotensinogen gene. Hypertension. 1999;33(1):108-15. DOI: 10.1161/01.HYP.33.1.10810.1161/01.HYP.33.1.1089931090Search in Google Scholar

15. Shiotani A, Sakakibara T, Yamanaka Y, Imamura H, Tarumi K, Manabe N, et al. Upper gastrointestinal ulcer in Japanese patients taking low-dose aspirin. J Gastroenterol. 2009; 44(2):126-31. DOI: 10.1007/s00535-008-2290-610.1007/s00535-008-2290-619214674Search in Google Scholar

16. Bregonzio C, Armando I, Ando H, Jezova M, Baiardi G, Saavedra JM. Anti-inflammatory effects of angiotensin II AT1 receptor antagonism prevent stress-induced gastric injury. Am J Physiol Gastrointest Liver Physiol. 2003;285(2):G414-23. DOI: 10.1152/ajpgi.00058.200310.1152/ajpgi.00058.200312686508Search in Google Scholar

17. Bregonzio C, Armando I, Ando H, Jezova M, Baiardi G, Saavedra M. Angiotensin II AT1 receptor blockade prevents gastric ulcers during cold-restraint stress. Ann N Y Acad Sci. 2004;1018:351-5. DOI: 10.1196/annals. 1296.044Search in Google Scholar

18. Carl-McGrath S, Grantzdorffer I, Lendeckel U, Ebert MP, Rocken C. Angiotensin II-generating enzymes, angiotensin-converting enzyme (ACE) and mast cell chymase (CMA1), in gastric inflammation may be regulated by H. pylori and associated cytokines. Pathology 2009;41:419-27. DOI: 10.1080/0031302090288503710.1080/0031302090288503719424904Search in Google Scholar

19. Seno K, Zhu JH, Barrett JD, Eggena P, Scremin OU, Lam K, et al. Cigarette smoke increases gastric ulcer size in part by an angiotensin II-mediated mechanism in rats. Dig Dis Sci. 1997;42:74-8. DOI: 10.1023/A:101888090420110.1023/A:1018880904201Search in Google Scholar

20. Wang PY, Chen HP, Chen A, Tsay FW, Lai KH, Kao SS, et al. Impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. Biomed Res Int. 2014; Article ID 616018, 6 pages. DOI: 10.1155/2014/61601810.1155/2014/616018416346725243161Search in Google Scholar

21. Masclee GM, Valkhoff VE, Coloma PM, de Ridder M, Romio S, Schuemie MJ, et al. Risk of upper gastrointestinal bleeding from different drug combinations. Gastroenterology. 2014;147(4):784-92. DOI: 10.1053/j.gastro.2014.06.007 10.1053/j.gastro.2014.06.00724937265Search in Google Scholar

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