Abstract:
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.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Silva PS,Fontana V,Luizon MR,Lacchini R,Silva WA Jr,Biagi C,Tanus-Santos JEdoi
10.1007/s00228-012-1326-2subject
Has Abstractpub_date
2013-02-01 00:00:00pages
167-77issue
2eissn
0031-6970issn
1432-1041journal_volume
69pub_type
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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abstract::Interaction of the main metabolites of diazepam and chlordiazepoxide with alcohol was measured in two subacute double-blind cross-over experiments on 40 healthy, young volunteers. The drugs were administered for two week periods. The variables measured were choice reaction time and accuracy, eye-hand co-ordination, di...
journal_title:European journal of clinical pharmacology
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abstract::In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels per...
journal_title:European journal of clinical pharmacology
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abstract::The plasma pharmacokinetics of adriamycin has been studied in 21 cancer patients (31-85 years old) without liver tumours after short (3.00 min) and prolonged (45 min-16 h) i.v. infusions. The area under the plasma concentration-time curve and the maximum plasma concentration compensated for dose variation showed a mor...
journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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abstract:OBJECTIVE:The multidrug resistance gene 1 (MDR1) seems to play a role in the carcinogenesis of colorectal tumors. The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined. METHODS:Two hundred and eighty-five colorectal cancer patie...
journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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abstract::The peripheral histamine-inhibiting and central sedative effects of single oral doses (SOD) and of repeated administration for one week (steady state, SS), of 20 mg hydroxyzine HCL and 10 mg cetirizine have been assessed in 12 healthy volunteers, in a double-blind placebo-controlled cross-over study. Peripheral H1-rec...
journal_title:European journal of clinical pharmacology
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