Genetic Variants in PTGS1 and NOS3 Genes Increase the Risk of Upper Gastrointestinal Bleeding: A Case-Control Study

Autor(es)

Forgerini, Marcela ^[1] ; Urbano, Gustavo ^[2] ; Nadai, Tales Rubens de ^[3] ; Batah, Sabrina Setembre ^[4] ; Fabro, Alexandre Todorovic ^[4] ; Mastroianni, Patricia de Carvalho ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Drugs & Med, Araraquara, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Surg, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Bauru Sch Dent, Dept Publ Hlth, Bauru, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol & Legal Med, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHARMACOLOGY; v. 12, JUL 5 2021.
• Citações Web of Science: 0

Resumo

Objective: To assess the association between PTGS1 and NOS3 variant alleles and the risk to develop upper gastrointestinal bleeding (UGIB) secondary to complicated peptic disease. Methods: A case-control study was conducted in a Brazilian complex hospital from July 2016 to March 2020. Case: Patients with UGIB diagnosis. Control: Patients admitted for surgery not related to gastrointestinal disorders. Variables: UGIB (outcome), genetic variants in PTGS1 and NOS3 genes (independent), and sex, age, schooling, ethnicity, previous history of gastrointestinal disorders, Helicobacter pylori serology, comorbidity, drug therapy, and lifestyle (confounding). The single-nucleotide polymorphisms (SNPs) of the PTSG1 gene (rs1330344, rs3842787, rs10306114, and rs5788) and NOS3 gene (rs2070744 and rs1799983) were determined using the real-time polymerase chain reaction. Helicobacter pylori serology was determined through the chemiluminescence technique. Logistic regression models were built and deviations of allelic frequencies from Hardy-Weinberg equilibrium were verified. Results: 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 (p-value: < 0.001); Helicobacter pylori infection (p-value: < 0.011); NSAIDs, LDA, and oral anticoagulant use (p-value: < 0.001); and alcohol intake (p-value: < 0.001) were also identified as independent risk factors for UGIB. Conclusion: 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. (AU)

• Processo FAPESP: 19/19591-5 - Perfil transcriptômico das áreas miofibroblásticas centradas em vias aéreas como potencial biomarcador das pneumonias intersticiais bronquiolocêntricas
• Beneficiário: Sabrina Setembre Batah
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/24193-3 - Determinantes genéticos da hemorragia gastrointestinal associada ao uso de ácido acetilsalicílico como agente antiplaquetário: um estudo de caso-controle
• Beneficiário: Patricia de Carvalho Mastroianni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07501-9 - Determinantes genéticos da hemorragia gastrointestinal associada ao uso do ácido acetilsalicílico como agente antiplaquetário: um estudo caso-controle
• Beneficiário: Marcela Forgerini
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto