Article

Aspirin-induced peptic ulcer and genetic polymorphisms

Department of Internal Medicine, Kawasaki Medical School, Matsushima Kurashiki City, Okayama, Japan.
Journal of Gastroenterology and Hepatology (Impact Factor: 3.5). 05/2010; 25 Suppl 1(s1):S31-4. DOI: 10.1111/j.1440-1746.2009.06212.x
Source: PubMed

ABSTRACT

There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.

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Available from: Akiko Shiotani, Sep 19, 2014
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    • "Increased production of IL-1 in the gastric mucosa might result in the enhanced suppression of gastric acid secretion, as well as enhanced inflammation, allowing the expansion of H. pylori colonization from the gastric antrum to the corpus. This event may lead to the development of hypochlorhydria, severe gastric atrophy, intestinal metaplasia, dysplasia and, ultimately, gastric carcinoma[17,20]. IL-1RN competitively binds to IL-1 receptors and counterbalances the potentially injurious proinflammatory effects of IL-1B[21,22]. "
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    ABSTRACT: Introduction: Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Methodology: Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. Results: It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B. No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. Conclusions: We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.
    Full-text · Article · Sep 2015
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    [Show abstract] [Hide abstract]
    ABSTRACT: There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.
    Full-text · Article · May 2010 · Journal of Gastroenterology and Hepatology
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    ABSTRACT: Antiplatelet therapy represents the cornerstone of treatment for the short- and long-term prevention of atherothrombotic disease processes, in particular in high-risk settings such as in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. Currently, dual antiplatelet therapy with aspirin and clopidogrel represents the most commonly used treatment regimen in these settings. However, a considerable number of patients continue to experience adverse outcomes, including both bleeding and recurrent ischemic events. Numerous investigations have demonstrated that this phenomenon may be, in part, attributed to the broad variability in individual response profiles to this standard antiplatelet treatment regimen, as identified by various assays of platelet function testing. In addition, recent studies have demonstrated that genetic polymorphisms may also have an important role in determining levels of platelet inhibition and may be considered as a tool to identify patients at risk of adverse events. This article provides an overview on antiplatelet drug response variability, an update on definitions, including the role of pharmacodynamic testing, underlying mechanisms - with emphasis on recent understandings on pharmacogenetics and drug-drug interactions - and current and future perspectives on individualized antiplatelet therapy.
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