PURPOSE: The antihypertensive effect of angiotensin-converting enzyme inhibitors (ACEi) is attributed partially to increased nitric oxide bioavailability. It is possible that functional polymorphisms in endothelial nitric oxide synthase (eNOS) and bradykinin receptor B2 (BDKRB2) genes may affect the antihypertensive response to enalapril. METHODS: We evaluated 106 hypertensive patients treated only with enalapril for 60 days. The difference between the mean arterial pressure (MAP) before and after the antihypertensive treatment was defined as ΔMAP. If ΔMAP were below or above the median value, the patients were classified as poor responders (PR) or good responders (GR), respectively. eNOS genotypes for the T(-786)C, G894T and 4b/4a polymorphisms were determined and haplotype frequencies were estimated by PHASE and Haplo.stats programs. The C(-58)T and BE1 +9/-9 polymorphisms of BDKRB2 genes and their haplotypes were determined by DNA sequencing. Robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. RESULTS: The TC/CC genotypes and the C allele for the eNOS T(-786)C polymorphism were more frequent in GR than in PR. Furthermore, the TT genotype for the BDKRB2 C(-58)T polymorphism was more frequent in PR than GR. No other significant differences in genotypes or haplotypes were found. However, we found significant gene-gene interactions: the CC genotype for the BDKRB2 C(-58)T polymorphism was associated with response to enalapril depending on eNOS T(-786)C genotypes. CONCLUSIONS: These findings suggest that eNOS T(-786)C and BDKRB2 C(-58)T polymorphisms may synergically affect the antihypertensive response to enalapril.
PURPOSE: The antihypertensive effect of angiotensin-converting enzyme inhibitors (ACEi) is attributed partially to increased nitric oxide bioavailability. It is possible that functional polymorphisms in endothelial nitric oxide synthase (eNOS) and bradykinin receptor B2 (BDKRB2) genes may affect the antihypertensive response to enalapril. METHODS: We evaluated 106 hypertensivepatients treated only with enalapril for 60 days. The difference between the mean arterial pressure (MAP) before and after the antihypertensive treatment was defined as ΔMAP. If ΔMAP were below or above the median value, the patients were classified as poor responders (PR) or good responders (GR), respectively. eNOS genotypes for the T(-786)C, G894T and 4b/4a polymorphisms were determined and haplotype frequencies were estimated by PHASE and Haplo.stats programs. The C(-58)T and BE1 +9/-9 polymorphisms of BDKRB2 genes and their haplotypes were determined by DNA sequencing. Robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. RESULTS: The TC/CC genotypes and the C allele for the eNOS T(-786)C polymorphism were more frequent in GR than in PR. Furthermore, the TT genotype for the BDKRB2 C(-58)T polymorphism was more frequent in PR than GR. No other significant differences in genotypes or haplotypes were found. However, we found significant gene-gene interactions: the CC genotype for the BDKRB2 C(-58)T polymorphism was associated with response to enalapril depending on eNOS T(-786)C genotypes. CONCLUSIONS: These findings suggest that eNOS T(-786)C and BDKRB2 C(-58)T polymorphisms may synergically affect the antihypertensive response to enalapril.
Authors: Aline S Marroni; Ingrid F Metzger; Debora C Souza-Costa; Sabrina Nagassaki; Valeria C Sandrim; Ronan X Correa; Fabricio Rios-Santos; Jose E Tanus-Santos Journal: Nitric Oxide Date: 2005-05 Impact factor: 4.427
Authors: M Nakayama; H Yasue; M Yoshimura; Y Shimasaki; K Kugiyama; H Ogawa; T Motoyama; Y Saito; Y Ogawa; Y Miyamoto; K Nakao Journal: Circulation Date: 1999-06-08 Impact factor: 29.690
Authors: Valéria C Sandrim; Roger W C de Syllos; Hugo R K Lisboa; Glaucia S Tres; Jose E Tanus-Santos Journal: Atherosclerosis Date: 2006-01-20 Impact factor: 5.162
Authors: Y Miyamoto; Y Saito; M Nakayama; Y Shimasaki; T Yoshimura; M Yoshimura; M Harada; N Kajiyama; I Kishimoto; K Kuwahara; J Hino; E Ogawa; I Hamanaka; S Kamitani; N Takahashi; R Kawakami; K Kangawa; H Yasue; K Nakao Journal: Hum Mol Genet Date: 2000-11-01 Impact factor: 6.150
Authors: Vivian Vasconcellos; Riccardo Lacchini; Anna L B Jacob-Ferreira; Maria L Sales; Maria C Ferreira-Sae; Roberto Schreiber; Wilson Nadruz; Jose E Tanus-Santos Journal: DNA Cell Biol Date: 2010-04 Impact factor: 3.311
Authors: M R Luizon; A C T Palei; V A Belo; L M Amaral; R Lacchini; G Duarte; R C Cavalli; V C Sandrim; J E Tanus-Santos Journal: Pharmacogenomics J Date: 2016-05-10 Impact factor: 3.550
Authors: G H Oliveira-Paula; R Lacchini; V Fontana; P S Silva; C Biagi; Jose E Tanus-Santos Journal: Eur J Clin Pharmacol Date: 2015-05-24 Impact factor: 2.953
Authors: Daniela A Pereira; Valeria C Sandrim; Ana C Palei; Lorena M Amaral; Vanessa A Belo; Riccardo Lacchini; Ricardo C Cavalli; Jose E Tanus-Santos; Marcelo R Luizon Journal: Pharmacogenomics Date: 2021-05-04 Impact factor: 2.638
Authors: Vanessa Fontana; Caitrin W McDonough; Yan Gong; Nihal M El Rouby; Ana Caroline C Sá; Kent D Taylor; Y-D Ida Chen; John G Gums; Arlene B Chapman; Stephen T Turner; Carl J Pepine; Julie A Johnson; Rhonda M Cooper-DeHoff Journal: J Am Heart Assoc Date: 2014-11-10 Impact factor: 5.501