European Journal of Clinical Pharmacology

, Volume 71, Issue 8, pp 949–957 | Cite as

Polymorphisms in VEGFA gene affect the antihypertensive responses to enalapril

  • G. H. Oliveira-Paula
  • R. Lacchini
  • V. Fontana
  • P. S. Silva
  • C. Biagi
  • Jose E. Tanus-Santos



Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that affects blood pressure by promoting vasodilation mediated by nitric oxide. Angiotensin-converting enzyme inhibitors (ACEi) up-regulate the VEGF expression; thus, genetic polymorphisms in the VEGFA gene could affect the antihypertensive responses to these drugs.


Hypertensive patients (n = 102) were prospectively treated only with the ACEi enalapril for 60 days. We compared the effect of VEGFA polymorphisms on changes in blood pressure after enalapril treatment. In addition, multiple linear regression analysis was carried out to assess the effect of covariates on blood pressure. Genotypes for g.-2578C>A (rs699947), g.-1154G>A (rs1570360), and g.-634G>C (rs2010963) VEGFA polymorphisms were determined, and haplotype frequencies were estimated.


Individuals carrying the CA and AA genotypes for the g.-2578C>A polymorphism and the AGG haplotype showed more intense decrease in blood pressure in response to enalapril 20 mg/day. A multiple linear regression analysis showed that the AA genotype for the g.-2578C>A polymorphism and the AGG haplotype are associated with more intense decrease in blood pressure in response to enalapril 20 mg/day, while the CC genotype for the g.-2578C>A polymorphism and the CGG haplotype are associated with the opposite effect.


These findings suggest that polymorphisms in VEGFA gene may affect the antihypertensive responses to enalapril.


Enalapril Haplotypes Hypertension Polymorphisms VEGFA 


Compliance with ethical standards


This study was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

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Table S1 (DOCX 16 kb)
228_2015_1872_MOESM2_ESM.docx (16 kb)
Table S2 (DOCX 16 kb)
228_2015_1872_MOESM3_ESM.docx (16 kb)
Table S3 (DOCX 15 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • G. H. Oliveira-Paula
    • 1
  • R. Lacchini
    • 2
  • V. Fontana
    • 3
  • P. S. Silva
    • 4
  • C. Biagi
    • 5
  • Jose E. Tanus-Santos
    • 1
  1. 1.Department of Pharmacology, Faculty of Medicine of Ribeirao PretoUniversity of Sao PauloRibeirao PretoBrazil
  2. 2.Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of NursingUniversity of Sao PauloRibeirao PretoBrazil
  3. 3.Brazilian Biosciences National Laboratory, CNPEMCampinasBrazil
  4. 4.Department of Pharmacy, Faculty of PharmacyFederal University of Juiz de ForaGovernador ValadaresBrazil
  5. 5.Santa Casa de AraçatubaAraçatubaBrazil

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