Forgerini Marcela, Urbano Gustavo, de Nadai Tales Rubens, Batah Sabrina Setembre, Fabro Alexandre Todorovic, Mastroianni Patrícia de Carvalho
Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil.
Department of Surgery, School of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
Front Pharmacol. 2021 Jul 5;12:671835. doi: 10.3389/fphar.2021.671835. eCollection 2021.
To assess the association between and variant alleles and the risk to develop upper gastrointestinal bleeding (UGIB) secondary to complicated peptic disease. A case-control study was conducted in a Brazilian complex hospital from July 2016 to March 2020. Patients with UGIB diagnosis. Patients admitted for surgery not related to gastrointestinal disorders. Variables: UGIB (outcome), genetic variants in and genes (independent), and sex, age, schooling, ethnicity, previous history of gastrointestinal disorders, serology, comorbidity, drug therapy, and lifestyle (confounding). The single-nucleotide polymorphisms (SNPs) of the gene (rs1330344, rs3842787, rs10306114, and rs5788) and gene (rs2070744 and rs1799983) were determined using the real-time polymerase chain reaction. serology was determined through the chemiluminescence technique. Logistic regression models were built and deviations of allelic frequencies from - equilibrium were verified. 200 cases and 706 controls were recruited. Carriers of the AG genotype of rs10306114 (OR: 2.55, CI 95%: 1.13-5.76) and CA + AA genotypes of rs5788 (OR: 2.53, CI 95%: 1.14-5.59) 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 (-value: < 0.001); infection (-value: < 0.011); NSAIDs, LDA, and oral anticoagulant use (-value: < 0.001); and alcohol intake (-value: < 0.001) were also identified as independent risk factors for UGIB. 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.
评估[具体基因名称1]和[具体基因名称2]变异等位基因与因复杂性消化性疾病继发上消化道出血（UGIB）风险之间的关联。2016年7月至2020年3月在巴西一家综合医院进行了一项病例对照研究。纳入UGIB诊断患者以及因非胃肠道疾病接受手术的患者。变量：UGIB（结局）、[具体基因名称1]和[具体基因名称2]基因中的基因变异（独立变量）以及性别、年龄、受教育程度、种族、既往胃肠道疾病史、[相关病原体]血清学、合并症、药物治疗和生活方式（混杂因素）。使用实时聚合酶链反应确定[具体基因名称1]基因（rs1330344、rs3842787、rs10306114和rs5788）和[具体基因名称2]基因（rs2070744和rs1799983）的单核苷酸多态性（SNP）。通过化学发光技术测定[相关病原体]血清学。构建逻辑回归模型并验证等位基因频率与哈迪-温伯格平衡的偏差。招募了200例病例和706例对照。rs10306114的AG基因型携带者（比值比：2.55，95%置信区间：1.13 - 5.76）和rs5788的CA + AA基因型携带者（比值比：2.53，95%置信区间：1.14 - 5.59）与UGIB发生风险增加相关。在非甾体抗炎药（NSAIDs）使用者中，评估的六个变异改变了UGIB风险的大小，而在低剂量阿司匹林（LDA）使用者中，其中四个变异（rs1330344、rs10306114、rs2070744和rs1799983）使UGIB风险增加。个人溃疡病史（P值：< 0.001）；[相关病原体]感染（P值：< 0.011）；NSAIDs、LDA和口服抗凝剂使用（P值：< 0.001）；以及饮酒（P值：< 0.001）也被确定为UGIB的独立危险因素。本研究在UGIB范围内进行了两项前所未有的分析（rs10306114和rs2070744），我们的研究结果表明，无论药物暴露情况如何，基因变异rs10306114和rs5788的存在都会增加UGIB风险。此外，评估变异的存在可能会改变LDA/NSAIDs使用者中UGIB风险的大小。因此，我们的数据表明需要进行个性化治疗和药物使用监测，以提高患者安全性。
