CYP2C19 loss-of-function alleles are not associated with higher prevalence of gastrointestinal bleeds in those who have been prescribed antidepressants: Analysis in a British-South Asian cohort
CYP2C19 loss-of-function alleles are not associated with higher prevalence of gastrointestinal bleeds in those who have been prescribed antidepressants: Analysis in a British-South Asian cohort
复制标题
CYP2C19 功能丧失等位基因与服用抗抑郁药的患者胃肠道出血患病率较高无关：英国-南亚队列分析
DOI：
10.1111/bcp.15762
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发表时间：
2023
影响因子：
3.4
通讯作者：
Magavern E
中科院分区：
文献类型：
--
作者：
Magavern E
CYP 2C 19是一种肝酶，参与抗抑郁药的代谢，与胃肠道出血（GIB）风险增加相关。我们的研究的目的是探讨功能丧失CYP 2C 19基因型和GIB在南亚血统的参与者处方antidepressants.MethodsGenes & Health参与者与Barts Health NHS Trust（N 22 753）的记录之间可能存在的关联，采用横断面方法进行了研究。Fisher精确检验用于比较不同代谢者类别中GIB的患病率。采用多变量回归分析方法，对抗抑郁药处方与GIB、CYP 2C 19代谢状态与GIB的相关性进行分析。共有864名参与者（4%）患有GIB; 534名（62%）被处方了CYP 2C 19代谢的抗抑郁药。抗抑郁药处方与GIB事件之间存在独立相关性（比值比1.8，置信区间1.5 - 2.0，P < 0.0001）。在未校正的分析中，CYP 2C 19推断的弱（P0.56）或中间（P0.53）代谢者状态与处方抗抑郁药的患者的GIB之间无相关性。多变量logistic回归模型未显示CYP 2C 19代谢不良（P0. 54）或中度（P0. 62）与GIB之间的独立相关性。结论CYP 2C 19依赖性抗抑郁药与GIB患病率增加相关。在服用抗抑郁药的个体中，GIB似乎与CYP 2C 19代谢者基因型无关。仅基于CYP 2C 19遗传信息的精确给药不太可能降低GIB患病率。
AimsCYP2C19 is a hepatic enzyme involved in the metabolism of antidepressants associated with increased gastrointestinal bleed (GIB) risk. The aim of our study was to explore a possible association between loss‐of‐functionCYP2C19genotypes and GIB in South Asian ancestry participants prescribed antidepressants.MethodsGenes & Health participants with a record in Barts Health NHS Trust (N 22 753) were studied using a cross‐sectional approach.CYP2C19diplotypes were assessed and metabolizer type inferred from consortia guidance. Fisher's exact test was used to compare the prevalence of GIB in different metabolizer categories. Multivariable regression was used to test for association between antidepressant prescriptions and GIB, and between CYP2C19 metabolizer state and GIB in the subcohort prescribed antidepressants.ResultsAntidepressants were frequently prescribed (47%,N= 10 612). A total of 864 participants (4%) had a GIB; 534 (62%) had been prescribed a CYP2C19 metabolized antidepressant. There was an independent association between antidepressant prescriptions and GIB events (odds ratio 1.8, confidence interval 1.5‐2.0,P< 0.0001). There was no relationship between CYP2C19 inferred poor (P0.56) or intermediate (P0.53) metabolizer status and GIB in those prescribed an antidepressant in unadjusted analysis. A multivariable logistic regression model did not show an independent association between poor (P0.54) or intermediate (P0.62) CYP2C19 metabolizers and GIB in the subcohort prescribed antidepressants.ConclusionsCYP2C19 dependent antidepressants are associated with increased GIB prevalence. GIB appeared independent fromCYP2C19metabolizer genotype in individuals who had been prescribed antidepressants. Precision dosing based onCYP2C19genetic information alone is unlikely to reduce GIB prevalence.