IK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitor

Autor(es)

Quintanilha, Julia C. F. ^[1] ; Racioppi, Alessandro ^[1] ; Wang, Jin ^[2] ; Etheridge, Amy S. ^[1] ; Denning, Stefanie ^[1] ; Pena, Carol E. ^[3] ; Skol, Andrew D. ^[4] ; Crona, Daniel J. ^{[5, 1, 6]} ; Lin, Danyu ^[2] ; Innocenti, Federico ^[1]

Afiliação do(s) autor(es)

^[1] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Eshelman Sch Pharm, Chapel Hill, NC 27515 - USA

^[2] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 - USA

^[3] Bayer Hlth Care Pharmaceut, Whippany, NJ - USA

^[4] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 - USA

^[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 - USA

^[6] Univ N Carolina, Dept Pharm, Med Ctr, Chapel Hill, NC 27515 - USA

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOGENOMICS JOURNAL; v. 22, n. 1 NOV 2021.
• Citações Web of Science: 1

Resumo

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 Identifier:NCT00073307 (TARGET). (AU)

• Processo FAPESP: 18/04491-2 - Suscetibilidade genética a toxicidades graves e mortes devido a toxicidades entre 1.626 pacientes com câncer tratados com bevacizumab: implicações para o tratamento e terapia personalizada
• Beneficiário: Júlia Coelho França Quintanilha
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado