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Pharmacol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> To assess the association between <jats:italic>PTGS1<\/jats:italic> and <jats:italic>NOS3<\/jats:italic> variant alleles and the risk to develop upper gastrointestinal bleeding (UGIB) secondary to complicated peptic disease.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A case\u2013control study was conducted in a Brazilian complex hospital from July 2016 to March 2020. <jats:italic>Case:<\/jats:italic> Patients with UGIB diagnosis. <jats:italic>Control:<\/jats:italic> Patients admitted for surgery not related to gastrointestinal disorders. Variables: UGIB (outcome), genetic variants in <jats:italic>PTGS1<\/jats:italic> and <jats:italic>NOS3<\/jats:italic> genes (independent), and sex, age, schooling, ethnicity, previous history of gastrointestinal disorders, <jats:italic>Helicobacter pylori<\/jats:italic> serology, comorbidity, drug therapy, and lifestyle (confounding). The single-nucleotide polymorphisms (SNPs) of the <jats:italic>PTSG1<\/jats:italic> gene (rs1330344, rs3842787, rs10306114, and rs5788) and <jats:italic>NOS3<\/jats:italic> gene (rs2070744 and rs1799983) were determined using the real-time polymerase chain reaction. <jats:italic>Helicobacter pylori<\/jats:italic> serology was determined through the chemiluminescence technique. Logistic regression models were built and deviations of allelic frequencies from <jats:italic>Hardy<\/jats:italic>\u2013<jats:italic>Weinberg<\/jats:italic> equilibrium were verified.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> 200 cases and 706 controls were recruited. Carriers of the AG genotype of rs10306114 (OR: 2.55, CI 95%: 1.13\u20135.76) and CA + AA genotypes of rs5788 (OR: 2.53, CI 95%: 1.14\u20135.59) were associated with an increased risk for the UGIB development. In nonsteroidal anti-inflammatory drugs (NSAIDs) users, the six variants evaluated modified the magnitude of the risk of UGIB, whereas in low-dose aspirin (LDA) users, an increased risk of UGIB was observed for four of them (rs1330344, rs10306114, rs2070744, and rs1799983). Personal ulcer history (<jats:italic>p<\/jats:italic>-value: &amp;lt; 0.001); <jats:italic>Helicobacter pylori<\/jats:italic> infection (<jats:italic>p<\/jats:italic>-value: &amp;lt; 0.011); NSAIDs, LDA, and oral anticoagulant use (<jats:italic>p<\/jats:italic>-value: &amp;lt; 0.001); and alcohol intake (<jats:italic>p<\/jats:italic>-value: &amp;lt; 0.001) were also identified as independent risk factors for UGIB.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study presents two unprecedented analyses within the scope of the UGIB (rs10306114 and rs2070744), and our findings showing an increased risk of UGIB in the presence of the genetic variants rs10306114 and rs5788, regardless of the drug exposure. Besides, the presence of the evaluated variants might modify the magnitude of the risk of UGIB in LDA\/NSAIDs users. Therefore, our data suggest the need for a personalized therapy and drug use monitoring in order to promote patient safety.<\/jats:p>","DOI":"10.3389\/fphar.2021.671835","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T08:11:30Z","timestamp":1625472690000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetic Variants in PTGS1 and NOS3 Genes Increase the Risk of Upper Gastrointestinal Bleeding: A Case\u2013Control Study"],"prefix":"10.3389","volume":"12","author":[{"given":"Marcela","family":"Forgerini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Urbano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tales Rubens de","family":"Nadai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina Setembre","family":"Batah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre Todorovic","family":"Fabro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia de Carvalho","family":"Mastroianni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"501","DOI":"10.2217\/pgs.15.6","article-title":"Pharmacogenomics of Cyclooxygenases","volume":"16","author":"Ag\u00fandez","year":"2015","journal-title":"Pharmacogenomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1089\/gtmb.2014.0261","article-title":"Role of Prostaglandins in Gastroprotection and Gastric Adaptation","volume":"56","author":"Brzozowski","year":"2005","journal-title":"J. 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