ABSTRACT Objective The use of acetylsalicylic acid, even in low doses, may be associated with the onset of upper gastrointestinal bleeding as an idiosyncratic response. Considering the role of the genetic background in inter-individual responses to pharmacotherapy, we aimed to investigate the role of seven variants in the TNF-α, IL-β, and IL-1RN genes in association with the risk of upper gastrointestinal bleeding in users of low-dose acetylsalicylic acid for the prevention of cardiovascular events. Methods A case-control study was conducted in a Brazilian hospital complex. The Case Group comprised patients diagnosed with upper gastrointestinal bleeding who were administered a low dose of acetylsalicylic acid (n=50). Two Control Groups were recruited: 1) low-dose acetylsalicylic acid users without gastrointestinal complaints and under the supervision of a cardiologist (n=50) and 2) healthy controls (n=189). Sociodemographic, clinical, pharmacotherapeutic, and lifestyle data were recorded through face-to-face interviews. Genomic DNA from all participants was genotyped for rs16944 and rs1143634 (IL-β gene), rs4251961 (IL-1RN gene), and rs1799964, rs1799724, rs361525, and rs1800629 (TNF-α gene). Results No significant difference was noted in the genotypic frequencies of TNF-α, IL-β, and IL-1RN variants between the Case and Control Groups of low-dose acetylsalicylic acid users (p>0.05). The frequency of rs1800629 genotypes (TNF-α gene) differed significantly between the Case Group and healthy controls (p=0.003). None of the evaluated variants were associated with a risk of upper gastrointestinal bleeding. Conclusion This study aimed to explore pharmacogenomics biomarkers in low-dose acetylsalicylic acid users. Our data suggest that the presence of IL-1β, IL-1RN, and TNF-α variants was not associated with an increased risk of upper gastrointestinal bleeding. doses response interindividual inter individual pharmacotherapy TNFα, TNFα TNF α, α ILβ, ILβ IL β, β IL-β IL1RN ILRN 1RN RN lowdose events casecontrol case control complex n=50. n50 n n=50 . 50 recruited 1 (n=50 2 n=189. n189 n=189 189 (n=189) Sociodemographic clinical pharmacotherapeutic facetoface face interviews rs rs1694 rs114363 gene, gene , rs425196 rs1799964 rs1799724 rs361525 rs180062 gene. p>0.05. p005 p p>0.05 0 05 (p>0.05) p=0.003. p0003 p=0.003 003 (p=0.003) IL1β, IL1β 1β, 1β IL-1β IL1RN, 1RN, n5 n=5 5 (n=5 n18 n=18 18 (n=189 rs169 rs11436 rs42519 rs179996 rs179972 rs36152 rs18006 p00 p>0.0 (p>0.05 p000 p=0.00 00 (p=0.003 n= (n= n1 n=1 (n=18 rs16 rs1143 rs4251 rs17999 rs17997 rs3615 rs1800 p0 p>0. (p>0.0 p=0.0 (p=0.00 (n (n=1 rs1 rs114 rs425 rs1799 rs361 rs180 p>0 (p>0. p=0. (p=0.0 rs11 rs42 rs179 rs36 rs18 p> (p>0 p=0 (p=0. rs4 rs17 rs3 (p> p= (p=0 (p (p=