期刊
PHARMACOGENOMICS
卷 9, 期 10, 页码 1419-1427出版社
FUTURE MEDICINE LTD
DOI: 10.2217/14622416.9.10.1419
关键词
fosinopril; genetics; high blood pressure; pharmacogenomics; RAAS
资金
- MIUR [FIRB #RBNE01724C]
- Regione Sardegna Progetti di Educazione Sanitaria [621]
- Italian Ministry of University and Research and Regione Sardegna
Aim: No definite factors predict blood pressure response to angiotensin-converting enzyme-inhibitors. The aim of this study was to test the association of gene polymorphisms of the renin-angiotensin-aldosterone system with essential hypertension and anthropometric variables, intermediate phenotypes and gene polymorphisms with blood pressure after fosinopril in a genetically homogeneous cohort. Methods: A total of 630 essential hypertension patients, not previously treated or out of antihypertensive treatment for at least 6 months versus 219 normotensives (genotype frequencies, chi(2)). A total of 191 patients were randomly assigned to fosinopril 20 mg/day. Samples for plasma renin activity and aldosterone, 24-h urinary sodium (flame photometry) were collected. Gene polymorphisms - angiotensin-converting enzyme (insertion/deletion), angiotensin II type 1-receptor (A1166C), aldosterone synthase (-344C/T) and angiotensinogen (-6A/G) - were analyzed by standard techniques. The association of anthropometric variables, intermediate phenotypes and gene polymorphisms with blood pressure after 4 weeks therapy was tested by univariate analysis and analysis of covariance model (intercooled Stata SE 9.2). Results: No genetic polymorphisms were associated with essential hypertension, blood pressure response and intermediate phenotypes (p > 0.05). Systolic blood pressure after therapy was associated with baseline systolic blood pressure, age and sex. Conclusions: Our results confirm the difficulty in dissecting both essential hypertension and pharmacogenomics when analyzing the effect of single genes in complex multifactorial traits.
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