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NAT2 乙酰化状态与柳氮磺吡啶不良反应的关系:系统评价和荟萃分析。

The association between NAT2 acetylator status and adverse drug reactions of sulfasalazine: a systematic review and meta-analysis.

机构信息

Division of Life and Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea.

College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea.

出版信息

Sci Rep. 2020 Feb 27;10(1):3658. doi: 10.1038/s41598-020-60467-8.

Abstract

N-acetyltransferase 2 (NAT2) acetylator status can be classified into three groups depending on the number of rapid alleles (e.g., NAT2*4): rapid, intermediate, and slow acetylators. Such acetylator status may influence the occurrence of adverse drug reactions (ADRs) during sulfasalazine treatment. This systematic review and meta-analysis aimed to evaluate the association between NAT2 acetylator status and ADRs of sulfasalazine. We searched for qualified studies in PubMed, Web of Science, Embase, and the Cochrane Library. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between NAT2 acetylator status and ADRs of sulfasalazine. Nine cohort studies involving 1,077 patients were included in the meta-analysis. NAT2 slow acetylators were associated with an increase in overall ADRs (OR 3.37, 95% CI: 1.43 to 7.93; p = 0.005), discontinuation due to overall ADRs (OR 2.89, 95% CI: 1.72 to 4.86; p < 0.0001), and dose-related ADRs (OR 5.20, 95% CI: 2.44 to 11.08; p < 0.0001), compared with rapid and intermediate acetylators. In conclusion, NAT2 slow acetylators are at risk of ADRs during sulfasalazine treatment. Based on our findings, NAT2 genotyping may be useful to predict the occurrence of ADRs during sulfasalazine treatment.

摘要

N-乙酰基转移酶 2(NAT2)乙酰化状态可根据快速等位基因(如 NAT2*4)的数量分为三组:快速、中间和缓慢乙酰化者。这种乙酰化状态可能会影响柳氮磺胺吡啶治疗期间不良反应(ADR)的发生。本系统评价和荟萃分析旨在评估 NAT2 乙酰化状态与柳氮磺胺吡啶 ADR 之间的关系。我们在 PubMed、Web of Science、Embase 和 Cochrane Library 中搜索合格的研究。计算比值比(OR)和 95%置信区间(CI)来评估 NAT2 乙酰化状态与柳氮磺胺吡啶 ADR 之间的关联强度。荟萃分析纳入了 9 项队列研究共 1077 名患者。NAT2 慢乙酰化者发生总体 ADR 的风险增加(OR 3.37,95%CI:1.43 至 7.93;p=0.005)、因总体 ADR 而停药的风险增加(OR 2.89,95%CI:1.72 至 4.86;p<0.0001)和剂量相关的 ADR 风险增加(OR 5.20,95%CI:2.44 至 11.08;p<0.0001),与快速和中间乙酰化者相比。总之,NAT2 慢乙酰化者在柳氮磺胺吡啶治疗期间有发生 ADR 的风险。基于我们的发现,NAT2 基因分型可能有助于预测柳氮磺胺吡啶治疗期间 ADR 的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f200/7046788/a2144eb8a9b7/41598_2020_60467_Fig1_HTML.jpg

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