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[Therapeutic implications of ACE-gene polymorphism]
Lida Dimopoulos-Xicki1, Martin Haas
1Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Osterreich.
Wiener Medizinische Wochenschrift (1946)
|March 29, 2005
Summary
Angiotensin converting enzyme (ACE) levels vary by genotype, influencing ACE-inhibitor therapy. Larger studies are needed to confirm if genotype testing optimizes treatment for the renin-angiotensin-aldosterone system.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Biochemistry
Background:
- Serum angiotensin converting enzyme (ACE) levels exhibit significant inter-individual variability.
- This variability is primarily attributed to genetic polymorphisms in the ACE gene, leading to distinct genotypes (DD, ID, II) associated with high, intermediate, and low ACE concentrations, respectively.
- Understanding these genotype-phenotype relationships is crucial for personalized medicine.
Purpose of the Study:
- To evaluate the potential of pre-therapeutic determination of angiotensin converting enzyme (ACE) genotype to optimize treatment strategies.
- To assess the efficacy of genotype-guided therapy with ACE-inhibitors and angiotensin II blockers.
- To address the existing controversies and limitations in current research regarding ACE genotype and therapeutic response.
Main Methods:
- Review and synthesis of existing interventional studies investigating the impact of ACE genotype on therapeutic outcomes.
- Analysis of patient cohorts from multiple studies to identify trends and discrepancies.
- Focus on therapies targeting the renin-angiotensin-aldosterone system.
Main Results:
- Numerous interventional studies have been conducted, but often suffer from small patient numbers.
- Results from existing studies are frequently inconsistent and conflicting, hindering definitive conclusions.
- The direct clinical utility of routine ACE genotype testing for guiding therapy remains uncertain.
Conclusions:
- Current evidence is insufficient to recommend routine pre-therapeutic testing of angiotensin converting enzyme (ACE) genotype for optimizing therapy.
- Larger, multicenter studies are essential to resolve existing controversies and establish the clinical validity of genotype-guided treatment adjustments.
- Further research is warranted before implementing ACE genotype determination as a standard clinical practice for therapies modulating the renin-angiotensin-aldosterone system.