Genetic Risk of Diverticular Disease Predicts Early Stoppage of Nicorandil
Genetic Risk of Diverticular Disease Predicts Early Stoppage of Nicorandil
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DOI：
10.1002/cpt.1941
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发表时间：
2020-07-10
影响因子：
6.7
通讯作者：
Lang, Chim C.
中科院分区：
文献类型：
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作者：
Noyes, James D.;Mordi, Ify R.;Lang, Chim C.
在欧洲，胃肠道瘘已被广泛报告为尼可地尔治疗的不良反应。患有潜在憩室疾病的人最有可能出现这种副作用。在西方国家，憩室病非常普遍，临床上可能无症状。本研究旨在确定与尼可地尔早期停药相关的憩室病遗传风险评分（GRS），这是药物不耐受的替代标志物。对来自苏格兰泰赛德糖尿病遗传学审计和研究（GoDARTS）数据库的1，077例患者进行了病例对照研究。病例定义为具有< 9次尼可地尔处方且无可识别的停药原因（n = 230）。对照组有≥ 9个处方，治疗持续至死亡/研究结束或心肌梗死后停止。创建了两个憩室GRS，并用于逻辑回归模型。单硝酸异山梨酯用作对照分析。根据23个可复制基因座，憩室GRS升高的患者提前停止尼可地尔治疗的风险增加（单变量（比值比（OR）2.26; P = 0.04]，多变量（OR 3.96; P = 0.01））。当使用完整的42种憩室评分时，观察到类似的趋势，但未达到统计学显著性。异山梨醇对照分析未达到统计学显著性。我们的分析表明憩室GRS升高与尼可地尔治疗早期停止之间存在新的正相关性。
Gastrointestinal fistulation has been widely reported as an adverse effect of nicorandil therapy in Europe. People who have underlying diverticular disease are most at risk of this side effect. In Western countries, diverticular disease is highly prevalent and can be clinically silent. This study aimed to identify diverticular disease genetic risk scores (GRSs) associated with early nicorandil stoppage, a surrogate marker for drug intolerance. A case-control study was carried out on 1,077 patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) database. Cases were defined as having < 9 nicorandil prescriptions with no identifiable reason for stopping (n = 230). Controls had either >= 9 prescriptions, treatment continuation to death/study end or stoppage post-myocardial infarction. Two diverticular GRSs were created and used in logistic regression models. Isosorbide mononitrate was used as a control analysis. Patients with a raised diverticular GRS, based on 23 replicable loci, had increased risk of stopping nicorandil therapy early (univariate (odds ratio (OR) 2.26; P = 0.04], multivariate (OR 3.96; P = 0.01)). Similar trends were noted when using the full 42 variant diverticular score but statistical significance was not reached. The isosorbide control analysis did not reach statistical significance. Our analysis demonstrates a novel positive association between a raised diverticular GRS and early stoppage of nicorandil therapy.