Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista "Júlio de Mesquita Filho", Araraquara, SP, Brazil.
Einstein (Sao Paulo). 2024 Aug 26;22:eAO0746. doi: 10.31744/einstein_journal/2024AO0746. eCollection 2024.
Forgerini et al. investigated the role of seven genetic variants in the risk of upper gastrointestinal bleeding as an adverse drug reaction. In 289 participants (50 cases and 189 controls), the presence of seven variants in the IL-1β, IL-1RN, and TNF-α genes was not associated with susceptibility to acetylsalicylic acid-induced upper gastrointestinal bleeding. 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.
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).
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.
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.
Forgerini 等人研究了七种遗传变异在作为不良反应的上消化道出血风险中的作用。在 289 名参与者（50 例病例和 189 例对照）中，IL-1β、IL-1RN 和 TNF-α 基因中的七种变异的存在与乙酰水杨酸诱导的上消化道出血易感性无关。乙酰水杨酸的使用，即使是低剂量，也可能与作为特异反应的上消化道出血的发生有关。考虑到遗传背景在药物治疗个体间反应中的作用，我们旨在研究 TNF-α、IL-β 和 IL-1RN 基因中的七种变异与低剂量乙酰水杨酸用于预防心血管事件的使用者中上消化道出血风险的关联中的作用。
在巴西医院综合体中进行了病例对照研究。病例组包括被诊断为上消化道出血并接受低剂量乙酰水杨酸治疗的患者（n=50）。招募了两个对照组：1）低剂量乙酰水杨酸使用者，无胃肠道投诉，并接受心脏病专家的监督（n=50）和 2）健康对照者（n=189）。通过面对面访谈记录社会人口统计学、临床、药物治疗和生活方式数据。对所有参与者的基因组 DNA 进行 rs16944 和 rs1143634（IL-β 基因）、rs4251961（IL-1RN 基因）和 rs1799964、rs1799724、rs361525 和 rs1800629（TNF-α 基因）的基因分型。
低剂量乙酰水杨酸使用者的病例组和对照组之间 TNF-α、IL-β 和 IL-1RN 变异的基因型频率无显著差异（p>0.05）。病例组和健康对照组之间 rs1800629 基因型（TNF-α 基因）的频率差异有统计学意义（p=0.003）。评估的变异均与上消化道出血风险无关。
本研究旨在探讨低剂量乙酰水杨酸使用者的药物基因组学生物标志物。我们的数据表明，IL-1β、IL-1RN 和 TNF-α 变异的存在与上消化道出血风险的增加无关。
