Contribution of plasma levels of VEGF-A and angiopoietin-2 in addition to a genetic variant in KCNAB1 to predict the risk of bevacizumab-induced hypertension

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2024-07-12 DOI:10.1038/s41397-024-00342-1

Julia C. F. Quintanilha, William Kevin Kelly, Federico Innocenti

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Abstract

Bevacizumab-induced hypertension poses a therapeutic challenge and identifying biomarkers for hypertension can enhance therapy safety. Lower plasma levels of VEGF-A, angiopoietin-2, and rs6770663 in KCNAB1 were previously associated with increased risk of bevacizumab-induced hypertension. This study investigated whether these factors independently contribute to grade 2–3 bevacizumab-induced hypertension risk in 277 cancer patients (CALGB/Alliance 90401). Multivariable analyses assessed the independent association of each factor and hypertension. Likelihood ratio test (LRT) evaluated the explanatory significance of combining protein levels and rs6770663 in predicting hypertension. Boostrap was employed to assess the mediation effect of protein levels on the rs6770663 association with hypertension. Lower protein levels and rs6770663 were independently associated with increased hypertension risk. Adding rs6770663 to protein levels improved the prediction of hypertension (LRT p = 0.0002), with no mediation effect observed. Protein levels of VEGF-A, angiopoietin-2 and rs6770663 in KCNAB1 are independent risk factors and, when combined, may improve prediction of bevacizumab-induced hypertension. ClinicalTrials.gov Identifier: NCT00110214.

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除 KCNAB1 基因变异外，血浆中 VEGF-A 和血管生成素-2 水平也有助于预测贝伐珠单抗诱发高血压的风险。

贝伐珠单抗诱发的高血压是一项治疗挑战，而确定高血压的生物标志物可以提高治疗的安全性。血浆中较低水平的血管内皮生长因子-A、血管生成素-2和KCNAB1中的rs6770663与贝伐珠单抗诱发高血压的风险增加有关。本研究调查了这些因素是否对277名癌症患者（CALGB/Alliance 90401）的2-3级贝伐珠单抗诱发高血压风险有独立作用。多变量分析评估了各因素与高血压的独立关联。似然比检验（LRT）评估了结合蛋白质水平和 rs6770663 预测高血压的解释意义。Boostrap 被用来评估蛋白质水平对 rs6770663 与高血压关系的中介效应。较低的蛋白质水平和 rs6770663 与高血压风险的增加有独立关联。将 rs6770663 与蛋白质水平相加可改善对高血压的预测（LRT p = 0.0002），但未观察到中介效应。血管内皮生长因子-A、血管生成素-2和KCNAB1中的rs6770663的蛋白水平是独立的风险因素，如果结合使用，可提高贝伐珠单抗诱发高血压的预测能力。ClinicalTrials.gov Identifier：NCT00110214。

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.