PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors.
Pharmacogenomics J
; 22(1): 82-88, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34775477
ABSTRACT
No biomarkers are available to predict patients at risk of developing hypertension induced by VEGF-pathway inhibitors. This study aimed to identify predictive biomarkers of hypertension induced by these drugs using a discovery-replication approach. The discovery set included 140 sorafenib-treated patients (TARGET study) genotyped for 973 SNPs in 56 genes. The most statistically significant SNPs associated with grade ≥2 hypertension were tested for association with grade ≥2 hypertension in the replication set of a GWAS of 1039 bevacizumab-treated patients from four clinical trials (CALGB/Alliance). In the discovery set, rs444904 (G > A) in PIK3R5 was associated with an increased risk of sorafenib-induced hypertension (p = 0.006, OR = 3.88 95% CI 1.54-9.81). In the replication set, rs427554 (G > A) in PIK3R5 (in complete linkage disequilibrium with rs444904) was associated with an increased risk of bevacizumab-induced hypertension (p = 0.008, OR = 1.39, 95% CI 1.09-1.78). This study identified a predictive marker of drug-induced hypertension that should be evaluated for other VEGF-pathway inhibitors.ClinicalTrials.gov IdentifierNCT00073307 (TARGET).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fator A de Crescimento do Endotélio Vascular
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Fosfatidilinositol 3-Quinase
/
Hipertensão
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Assunto da revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos