Polymorphisms in VEGFA gene affect the antihypertensive responses to enalapril

• Published in: European journal of clinical pharmacology Vol. 71; no. 8; pp. 949 - 957
• Main Authors: Oliveira-Paula, G. H., Lacchini, R., Fontana, V., Silva, P. S., Biagi, C., Tanus-Santos, Jose E.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2015; Springer Nature B.V
• Subjects: Adult; Antihypertensive Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Blood Pressure - drug effects; Drug therapy; Enalapril - therapeutic use; Female; Genes; Genotype; Heart Rate - drug effects; Humans; Hypertension; Hypertension - drug therapy; Hypertension - genetics; Hypertension - physiopathology; Male; Middle Aged; Pharmacogenetics; Pharmacology/Toxicology; Polymorphism; Polymorphism, Genetic; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Haplotypes; Hypertension; Enalapril; Polymorphisms
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-015-1872-5

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