angiotensinogen and benazepril

This study examined the association between T1198C polymorphism of the angiotensinogen (AGT) gene and the blood pressure response to ACE inhibitors in a Chinese hypertensive cohort. After a 2-week single-blind placebo run-in period, benazepril (10-20 mg/day) or imidapril (5-10 mg/day) was administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. Polymerase chain reaction combined with restriction enzyme digestion was used to detect the polymorphism, and the patients were classified as having the TT, TC, or CC genotype. The achieved changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed to determine their association with genotypes at the AGT gene locus. In the total 509 patients, the TT genotype was observed in 44 patients (8.7%), the TC genotype in 214 patients (42.0%), and the CC genotype in 251 patients (49.3%). The SBP reductions in patients with the TT genotype, TC genotype, and CC genotype were -15.3+/-12.7 mmHg, -14.0+/-12.7 mmHg, and -14.4+/-12.4 mmHg, respectively (p=0.809). The DBP reductions in patients with the TT genotype, TC genotype, and CC genotype were -8.5+/-8.1 mmHg, -8.3+/-7.5 mmHg, and -8.9+/-6.6 mmHg, respectively (p=0.638). There were no significant differences in the changes in SBP or DBP after treatment among the three genotype groups. In conclusion, these results suggest that the AGT genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibitors in Chinese hypertensive patients.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Antihypertensive Agents; Benzazepines; Blood Pressure; China; Double-Blind Method; Female; Humans; Hypertension; Imidazolidines; Male; Middle Aged; Polymorphism, Genetic

Angiotensin-converting enzyme inhibitors are widely used antihypertensive drugs with individual response variation. We studied whether interactions of AGT, AGTR1 and ACE2 gene polymorphisms affect this response.. Our study is based on a 3-year field trial with 1831 hypertensive patients prescribed benazepril. Generalized multifactor dimensionality reduction was used to explore interaction models and logistic regressions were used to confirm them.. A two-locus model involving the AGT and ACE2 genes was found in males, the sensitive genotypes showed an odds ratio (OR) of 1.9 (95% CI: 1.3-2.8) when compared with nonsensitive genotypes. Two AGT-AGTR1 models were found in females, with an OR of 3.5 (95% CI: 2.0-5.9) and 3.1 (95% CI: 1.8-5.3).. Gender-specific gene-gene interactions of the AGT, AGTR1 and ACE2 genes were associated with individual variation of response to benazepril. Further studies are needed to confirm this finding.

Topics: Adult; Aged; Angiotensin-Converting Enzyme 2; Angiotensinogen; Antihypertensive Agents; Asian People; Benzazepines; Female; Gene Frequency; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Single Nucleotide; Receptor, Angiotensin, Type 1; Renin-Angiotensin System

To identify the genetic contribution to the variation in blood pressure (BP) response to angiotensin-converting enzyme inhibitors (ACEIs), single-nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT), angiotensin receptor 1 (AGTR1), and angiotensin receptor 2 (AGTR2) genes were evaluated for their association with BP response to ACEI in Chinese patients with hypertension in a 2-stage design.. We selected 1447 hypertensive patients from a 3-year benazepril postmarket surveillance trial and genotyped them for 14 SNPs in the AGT, AGTR1, and AGTR2 genes. The AGT rs7079 (C/T) SNP (3'-untranslated region) was significantly associated with the response of diastolic BP to benazepril (diastolic BP response: -7.4 mm Hg for subjects with the CC genotype, -8.9 mm Hg for CA, and -10.1 mm Hg for AA; P=0.001). Although there was no association of individual SNPs in the AGTR1 gene, there was a graded response between common haplotypes and systolic BP reduction in the order of haplotype 2 (H2)/lack of haplotype 3 (non-H3) (-13.6 mm Hg) > non-H2/non-H3 (-10.9 mm Hg) > H3/non-H2 (-6.6 mm Hg) (P=0.004). The total variations in response to ACEI therapy that were explained by the AGT SNP and AGTR1 haplotype groups were 13% for systolic and 9% to 9.6% for diastolic BP, respectively.. AGT SNP rs7079 and AGTR1 haplotypes were associated with BP reduction in response to ACEI therapy in hypertensive Chinese patients. This will be useful in future studies, providing genetic markers to predict the hypertensive response to ACEI therapy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Benzazepines; Blood Pressure; Female; Haplotypes; Humans; Hypertension; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2

To investigate the association between M235T variant of angiotensinogen (AGT) gene and the blood pressure response to benazepril in a hypertensive cohort.. Benazepril (10-20 mg/day) was administered for 6 weeks to 251 essential hypertensives. Polymerase chain reaction (PCR) combined with restriction enzyme digestion was used to detect the polymorphism and the patients were classified as MM, MT or TT genotype. The changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed for association with genotypes at the AGT gene locus.. The MM genotype was observed in 23 patients (9.2%), the MT genotype in 104 patients (41.4%) and the TT genotype in 124 patients (49.4%). There was no association between these polymorphisms and the blood pressure responses in the total 251 patients. But based on the analysis stratified by age, the association between these polymorphism and the DBP responses was found in the old patients (> or = 60 years old) subgroup, the reduction in DBP was significantly greater in patients carrying the MM compared to MT or TT genotypes (14.8 +/- 4.8 mm Hg vs. 7.9 +/- 7.7 mm Hg or 9.8 +/- 6.4 mm Hg respectively; ANOVA, P = 0.034).. The M235T polymorphism of the AGT gene was shown to influence the responses to benazepril in old hypertensive patients (> or = 60 years old). Thus, specific genotypes might predict the response to specific antihypertensive treatment.

Topics: Aged; Angiotensinogen; Antihypertensive Agents; Benzazepines; Female; Genotype; Humans; Hypertension; Male; Middle Aged; Polymorphism, Single Nucleotide