Clinical variables, not RAAS polymorphisms, predict blood pressure response to ACE inhibitors in Sardinians.

Abstract

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.

• Authors: Fabiana Filigheddu, Giuseppe Argiolas, Emanuela Bulla, Chiara Troffa, Patrizia Bulla, Simone Fadda, Roberta Zaninello, Simona Degortes, Francesca Frau, Silvia Pitzoi, Nicola Glorioso
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 9 Issue 10 Pg. 1419-27 (Oct 2008) ISSN: 1744-8042 [Electronic] England
• PMID: 18855530 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Fosinopril

Topics

• Adult
• Alleles
• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Anthropometry
• Blood Pressure (drug effects)
• Case-Control Studies
• Chi-Square Distribution
• Cohort Studies
• Female
• Fosinopril (therapeutic use)
• Gene Frequency
• Humans
• Hypertension (genetics, physiopathology)
• Italy
• Male
• Middle Aged
• Polymorphism, Genetic (drug effects)
• Renin-Angiotensin System (genetics)