Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases
Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases
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DOI：
10.1038/s41397-020-0151-8
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发表时间：
2020-02-04
影响因子：
2.8
通讯作者：
Salinas-Martinez, Ana Maria
中科院分区：
文献类型：
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作者：
Bermudez de Leon, Mario;Leon-Cachon, Rafael B. R.;Salinas-Martinez, Ana Maria
奥司他韦是一种前药，是治疗和预防流感爆发的最佳选择。然而，许多接受奥司他韦治疗的患者出现了不良反应，包括超敏反应、胃炎和神经系统症状。本研究的目的是确定墨西哥患者接受奥司他韦治疗的药物不良反应（ADR），以及这些ADR是否与奥司他韦代谢、转运和相互作用相关基因的SNP相关。这项研究招募了310名患有急性呼吸道疾病的墨西哥患者，并对他们进行了奥司他韦治疗（75毫克/天，持续5天），因为他们被怀疑患有甲型H1N1流感病毒感染。临床数据来自医疗记录和访谈。使用实时聚合酶链反应和TaqMan探针进行基因分型。根据遗传模型，用列联表和逻辑回归分析评估这种关联。在310例患者中，仅38例（12.25%）出现奥司他韦的ADR：超敏反应（1.9%）、胃炎（10%）和抑郁和焦虑（0.9%）。ABCB 1-rs 1045642基因多态性在隐性模型下与药物不良反应相关（P = 0.017），等位基因C与无药物不良反应相关，等位基因T与药物不良反应相关。SLC 15 A1-rs 2297322、ABCB 1-rs 2032582和CES 1-rs 2307243多态性不符合Hardy-Weinberg平衡，其余多态性未发现其他关联。总之，ABCB 1基因编码的转运蛋白多态性rs 1045642是奥司他韦治疗中ADR的潜在预测生物标志物。
Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy-Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.