Pharmacogenetics of Chronic Heart Failure – Beta Blockers

Overview

Background.
Activation of the renin-angiotensin (RAS) cascade and sympathetic nervous systems adversely affect heart failure progression. ACE deletion allele (ACE D) of insertion /deletion polymorphism in the gene coding for angiotensin-I converting enzyme is associated with increased renin-angiotensin activation. The aim of the study was to test pharmacogenetic associations of I/D ACE genotype with beta blockers therapy in patients with chronic heart failure. 

Methods and Results.
A total of 241 patients were included in the study, 63% with betablocker therapy and 37% without it. Using polymerase chain reaction (PCR) method, I/D genotype was detected in 2% agarose electrophoretic gel in UV light. Patients with chronic heart failure and with the II genotype of polymorphism I/D ACE were younger, with more frequent administration of betablockers and diuretics, with less regular administration of aspirin and with lower glycemia and plasma TNFα level. A significant difference in genotype distribution and allele frequency between patients with recommended dose and patients without betablockers therapy was proved, when a decrease of the D allele in patients with betablockers had been observed. Contemporary evaluating of AC inhibitor and betablocker therapy, a decrease of ID+DD genotypes in patients with lower than 50% recommended dose compared with the others was found. 

Conclusions.
In this study, we proved statistically significant interactions between genotypes in I/D ACE polymorphism, betablocker administration, its dosing and pharmacogenetic interaction with ACE inhibitors in patients with chronic heart failure. 

Key words:
I/D ACE polymorphism, therapy with beta blockers, AC inhibitors, pharmacogenetics