Abstract
Aims: The purpose of this study was to determine whether the deletion/insertion (D/I) polymorphism in the ACE-encoded angiotensin-converting enzyme or the pooled gene effect of five renin-angiotensin-aldosterone system (RAAS) polymorphisms were disease modifiers in a large cohort of unrelated patients with genotyped hypertrophic cardiomyopathy (HCM). Methods and results: Five different RAAS polymorphism genotypes were established by PCR amplification of the surrounding polymorphic regions of genomic DNA in a cohort of 389 unrelated patients comprehensively genotyped for HCM-causing mutations in eight sarcomeric/myofilament genes. Patient clinical data were archived in a database blinded both to the primary myofilament defect and the polymorphism genotype. Each patient was assessed with respect to ACE genotype as well as composite pro-left ventricular hypertrophy (LVH) RAAS polymorphism score (0-5). Overall, no clinical parameter correlated independently with ACE genotype. Subset analysis of the two most common genetic subtypes of HCM, MYBPC3 (myosin binding protein C) and MYH7 (beta myosin heavy chain), demonstrated a significant pro-LVH effect of DD-ACE only in patients with MYBPC3-HCM. In MYBPC3-HCM, left ventricular wall thickness was greater in patients with DD genotype (25.8 ± 5 mm) compared with DI (21.8 ± 4) or II genotype (20.8 ± 5, P = 0.01). Moreover, extreme hypertrophy (>30 mm) was only seen in MYBPC3-HCM patients who also hosted DD-ACE. An effect of RAAS pro-LVH score was evident only in the subgroup of patients with no previously identified myofilament mutation. Conclusion: This study demonstrates that RAAS genotypes may modify the clinical phenotype of HCM in a disease gene-specific fashion rather than indiscriminately.
Original language | English (US) |
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Pages (from-to) | 2457-2462 |
Number of pages | 6 |
Journal | European heart journal |
Volume | 26 |
Issue number | 22 |
DOIs | |
State | Published - Nov 2005 |
Keywords
- ACE polymorphism
- Genetic testing
- Hypertrophic cardiomyopathy
- Left ventricular hypertrophy
- Renin-angiotensin-aldosterone system
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine