目的:非甾体抗炎药(NSAIDs)是最常用的处方药,但是它们的使用可能与许多不良反应有关,包括上消化道病变。该研究的目的是确定与上消化道病变相关的临床和药物遗传因素,包括那些与NSAIDs有关的,多学科医院的病人。
方法:该研究包括92名患者(平均年龄59.4±16.5岁;47名女性),在住院治疗期间接受了食管胃十二指肠镜检查。考虑患者在住院前一年内摄入NSAIDs和胃保护剂。人口统计,临床,组间比较患者的实验室数据,包括使用实时PCR对CYP2C9*2rs179985,CYP2C9*3rs1057910,CYP2C8*3rs11572080,CYP2C8*3rs10509681,PTGS-1rs10306135,PTGS-1rs12353214和PTGS-2rs20417进行基因分型。
结果:在NSAIDs+患者中,PTGS1rs10306135AT+TT基因型使发生胃肠道并发症的机会增加5.4倍(95%CI=1.30-22.27)。在总样本中,吸烟(OR=3.12,95%CI=1.15-8.46),和酒精摄入量(OR=4.09,95%CI=1.05-15.87)增加胃肠道损伤的几率。在NSAIDs+奥美拉唑患者中,去年法莫替丁和法莫替丁和奥美拉唑与未服用胃保护剂一样无效;在总样本中,法莫替丁(OR=0.19,95%CI=0.04-0.93)和两种胃保护剂(OR=0.13,95%CI=0.02-0.75)降低了上消化道病变的机会.
结论:患者的药物遗传学特征可能与NSAIDs引起的上消化道损伤的发生有关。
OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications, but their use can be associated with a number of adverse reactions, including upper gastrointestinal lesions. The aim of the study was to identify clinical and pharmacogenetic factors associated with upper gastrointestinal lesions, including those linked to NSAIDs, in patients at a multidisciplinary hospital.
METHODS: The study included 92 patients (mean age 59.4±16.5 years; 47 women), who underwent esophagogastroduodenoscopy during inpatient treatment. Patients\' intake of NSAIDs and gastroprotectors during the year before hospitalization was considered. Demographic, clinical, laboratory data of patients were compared between groups, including genotyping for CYP2C9*2 rs179985, CYP2C9*3 rs1057910, CYP2C8*3 rs11572080, CYP2C8*3 rs10509681, PTGS-1 rs10306135, PTGS-1 rs12353214, and PTGS-2 rs20417 using real-time PCR.
RESULTS: In NSAIDs+ patients, PTGS1 rs10306135 AT+TT genotypes increased the chance of developing gastrointestinal complications by 5.4 times (95 % CI=1.30-22.27). In total sample, smoking (OR=3.12, 95 % CI=1.15-8.46), and alcohol intake (OR=4.09, 95 % CI=1.05-15.87) increased odds of gastrointestinal damage. In NSAIDs+ patients omeprazole, famotidine and both famotidine and omeprazole during the last year were as ineffective as not taking gastroprotectors; in total sample famotidine (OR=0.19, 95 % CI=0.04-0.93) and two gastroprotectors (OR=0.13, 95 % CI=0.02-0.75) reduced the chance of upper gastrointestinal lesions.
CONCLUSIONS: Pharmacogenetic features of patients may significantly contribute to the development NSAIDs-induced upper gastrointestinal injuries.