biostudies-literatureQuintanilha JCFNHGRI NIH HHSNCI NIH HHS82-88https://www.ebi.ac.uk/biostudies/studies/S-EPMC8799524biostudies-literatureUnknown22(1)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 The pharmacogenomics journalPIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors.PMC8799524U10 CA180882R01 HG009974P50 CA058223U24 CA196171R21 CA139280U10 CA180821UG1 CA233373K07 CA140390Quintanilha JCFDenning SLin DSkol ADInnocenti FEtheridge ASCrona DJPena CEWang JRacioppi AfalsePIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors.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 2022-01-01T00:00:00Z2022 Feb2026-05-08T01:49:44.34Z2025-04-19T22:48:34.075ZS-EPMC87995243477547710.1038/s41397-021-00261-5