Association of ticagrelor with risk of infection： a two-sample Mendelian randomization study based on the GWAS database

XU Guifeng; WU Yonglin; GUO Gongjie; HUANG Junhong; XIE Zhipeng; LUO Wenwei; ZHONG Shilong; LAI Weihua

doi:10.6039/j.issn.1001-0408.2023.07.17

您当前的位置：

首页 >

文章列表页 >

Association of ticagrelor with risk of infection： a two-sample Mendelian randomization study based on the GWAS database

更新时间：2024-02-19

- Association of ticagrelor with risk of infection： a two-sample Mendelian randomization study based on the GWAS database
- ZHONGGUO YAOFANG Vol. 34, Issue 7, Pages: 859-862(2023)
- 作者机构：
  
  1.华南理工大学医学院，广州　510006
  2.南方医科大学附属广东省人民医院/广东省医学科学院药学部，广州　510080
  3.南方医科大学药学院，广州　510515
  4.华南理工大学生物科学与工程学院，广州　510006
  5.南方医科大学附属广东省人民医院/广东省医学科学院冠心病防治研究重点实验室，广州　510080
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.07.17
  CLC： R972;R969.3
- Published：15 April 2023，
  
  Received：20 November 2022，
  
  Revised：26 December 2022，
扫描看全文
许桂锋,吴永麟,郭龚杰等.替格瑞洛与感染风险的关联：一项基于GWAS数据库的两样本孟德尔随机化研究 ^Δ[J].中国药房,2023,34(07):859-862.

XU Guifeng,WU Yonglin,GUO Gongjie,et al.Association of ticagrelor with risk of infection： a two-sample Mendelian randomization study based on the GWAS database[J].ZHONGGUO YAOFANG,2023,34(07):859-862.
许桂锋,吴永麟,郭龚杰等.替格瑞洛与感染风险的关联：一项基于GWAS数据库的两样本孟德尔随机化研究 ^Δ[J].中国药房,2023,34(07):859-862. DOI： 10.6039/j.issn.1001-0408.2023.07.17.

XU Guifeng,WU Yonglin,GUO Gongjie,et al.Association of ticagrelor with risk of infection： a two-sample Mendelian randomization study based on the GWAS database[J].ZHONGGUO YAOFANG,2023,34(07):859-862. DOI： 10.6039/j.issn.1001-0408.2023.07.17.

摘要

目的

探讨替格瑞洛与感染风险的因果关联。

方法

采用两样本孟德尔随机化方法。基于迄今为止最大规模的替格瑞洛及其主要活性代谢物AR-C124910XX体内暴露量的全基因组关联分析结果选取遗传工具变量。通过逆方差加权法孟德尔随机化模型分析替格瑞洛及其主要活性代谢物AR-C124910XX与药物适应证（冠状动脉疾病、不稳定型心绞痛、心肌梗死、卒中和缺血性卒中）的因果关系，作为遗传工具变量的阳性控制内容。进一步使用该方法分析替格瑞洛与细菌感染、急性下呼吸道感染、细菌性肺炎、肺炎、急性上呼吸道感染、脓毒症的因果关系，并用异质性检验、水平基因多效性检验来评估结果的稳健性。

结果

遗传代理的替格瑞洛稳态药时曲线下面积（AUCss）增加可以显著降低冠状动脉疾病、心肌梗死、不稳定型心绞痛的发生风险（

＜0.001），而其主要活性代谢物AR-C124910XX的AUCss遗传工具变量未能通过阳性控制。进一步分析显示，遗传代理的替格瑞洛AUCss的增加可以潜在地降低细菌感染[OR（95%CI）＝0.80（0.65，0.99），

＝0.040]和脓毒症[OR（95%CI）＝0.84（0.73，0.98），

＝0.023]的发生风险。异质性检验结果表明，遗传代理的替格瑞洛AUCss与细菌感染、脓毒症的因果关联不存在异质性（

＞0.05）。水平基因多效性检验结果表明，遗传代理的替格瑞洛AUCss与细菌感染、脓毒症的因果关联不存在水平基因多效性的影响（

＞0.05）。

结论

替格瑞洛具有潜在的降低脓毒症和细菌感染风险的作用。

Abstract

OBJECTIVE

To investigate the causal association between ticagrelor and risk of infection

METHODS

Two-sample Mendelian randomization was adopted. Genetic instrumental variables were selected based on the results of the largest genome-wide association analysis to

vivo

exposure of ticagrelor and its major active metabolite AR-C124910XX. The causal associations of ticagrelor and its major active metabolite AR-C124910XX with drug indications （coronary artery disease， unstable angina pectoris， myocardial infarction， stroke and ischemic stroke）were analyzed by inverse variance weighted Mendelian randomization model as a positive control for genetic instrumental variables. The causal relationship between ticagrelor and bacterial infection， acute lower respiratory infection， bacterial pneumoniae， pneumoniae， acute upper respiratory infection and sepsis were further analyzed by using this method， and the robustness of the results was assessed by using heterogeneity tests and horizontal pleiotropy tests.

RESULTS

The increase of area under the curve at steady state （AUCss） of the genetic surrogated ticagrelor significantly reduced the risk of coronary artery disease， myocardial infarction and unstable angina pectoris（

＜0.001）. AUCss genetic instrument variables of its main active metabolite AR-C124910XX failed to pass positive control. Further analysis showed that the increase of the genetic surrogated ticagrelor exposure suggestively reduced the risk of bacterial infection [OR（95%CI）＝0.80（0.65，0.99），

＝0.040] and sepsis [OR （95%CI）＝0.84（0.73， 0.98），

＝0.023]. The results of the heterogeneity tests showed that there was no heterogeneity in the causal association of the genetic surrogated ticagrelor AUCss with bacterial infection and sepsis （

＞0.05）. The results of horizontal pleiotropy tests showed that the causal association of genetic surrogated ticagrelor AUCss with bacterial infection and sepsis had no effects on horizontal pleiotropy （

＞0.05）.

CONCLUSIONS

Ticagrelor has a potential role in reducing the risk of sepsis and bacterial infections.

关键词

替格瑞洛感染孟德尔随机化全基因组关联分析因果推断脓毒症

Keywords

infectionMendelian randomizationgenome-wide association analysiscausal inferencesepsis

references

VIRANI S S，ALONSO A，BENJAMIN E J，et al. Heart disease and stroke statistics-2020 update：a report from the American Heart Association[J]. Circulation，2020，141（9）：e139-e596.

CAPODANNO D，ALFONSO F，LEVINE G N，et al. ACC/AHA versus ESC guidelines on dual antiplatelet therapy[J]. J Am Coll Cardiol，2018，72（23）：2915-2931.

STOREY R F，JAMES S K，SIEGBAHN A，et al. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study[J]. Platelets，2014，25（7）：517-525.

BUTT J H，FOSBØL E L，GERDS T A，et al. Ticagrelor and the risk of Staphylococcus aureus bacteraemia and other infections[J]. Eur Heart J Cardiovasc Pharmacother，2022，8（1）：13-19.

BLASCO-COLMENARES E，PERL T M，GUALLAR E，et al. Aspirin plus clopidogrel and risk of infection after coronary artery bypass surgery[J]. Arch Intern Med，2009，169（8）：788-796.

SMITH G D，HEMANI G. Mendelian randomization： genetic anchors for causal inference in epidemiological studies[J]. Hum Mol Genet，2014，23（R1）：R89-R98.

KHASAWNEH L Q，AL-MAHAYRI Z N，ALI B R. Mendelian randomization in pharmacogenomics：the unforeseen potentials[J]. Biomedecine Pharmacother，2022，150：112952.

VARENHORST C，ERIKSSON N，JOHANSSON Å，et al. Effect of genetic variations on ticagrelor plasma levels and clinical outcomes[J]. Eur Heart J，2015，36（29）：1901-1912.

BURGESS S，BUTTERWORTH A，THOMPSON S G. Mendelian randomization analysis with multiple genetic variants using summarized data[J]. Genet Epidemiol，2013，37（7）：658-665.

VERBANCK M，CHEN C Y，NEALE B，et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J]. Nat Genet，2018，50（5）：693-698.

BOWDEN J，DAVEY SMITH G，BURGESS S. Mendelian randomization with invalid instruments：effect estimation and bias detection through Egger regression[J]. Int J Epidemiol，2015，44（2）：512-525.

LI H L，FENG Q，TSOI M F，et al. Risk of infections in patients treated with ticagrelor vs. clopidogrel：a systematic review and meta-analysis[J]. Eur Heart J Cardiovasc Pharmacother，2021，7（3）：171-179.

RAHMAN M，GUSTAFSSON D，WANG Y Z，et al. Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis[J]. Platelets，2014，25（4）：257-263.

FONT M D，THYAGARAJAN B，KHANNA A K. Sepsis and septic shock：basics of diagnosis，pathophysiology and clinical decision making[J]. Med Clin North Am，2020，104（4）：573-585.

THOMAS M R，OUTTERIDGE S N，AJJAN R A，et al. Platelet P2Y12 inhibitors reduce systemic inflammation and its prothrombotic effects in an experimental human model[J]. Arterioscler Thromb Vasc Biol，2015，35（12）：2562-2570.

ALSHARIF K F，THOMAS M R，JUDGE H M，et al. Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and phagocytosis[J]. Vasc Pharmacol，2015，71：201-207.

LANCELLOTTI P，MUSUMECI L，JACQUES N，et al. Antibacterial activity of ticagrelor in conventional antiplatelet dosages against antibiotic-resistant gram-positive bacteria[J]. JAMA Cardiol，2019，4（6）：596-599.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

中西医结合方案治疗脓毒症的Meta分析

羟乙基淀粉在脓毒症患者中的应用及对肾功能影响的相关研究进展

乌司他丁对ICU脓毒症患者凝血功能障碍的影响

谷氨酰胺对脓毒症模型大鼠心肌细胞的保护作用

Study on Protective Mechanism of Dexmedetomidine on Cerebral Injury in Sepsis Model Rats Based on SIRT 1/ Akt/GSK3β/β-catenin Signaling Pathway

Related Author

张春燕刘洋冯婉玉

周丽嫔

王淑颖?应春晓?何许伟?张剑?

柴其翔韦四喜王娅婷方琴王季石

DONG Xiaoliu

SONG Lihua

DONG Wei

GAO Ming

Related Institution

No data

Address：8/F,129 Daping Main Street,Yuzhong District,Chongqing 400042,P.R.China
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰