title: [Pharmacogenetics of chronic heart failure--beta blockers].
abstract: 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-1 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.
  
  
  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 TNFalpha 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.
authors.affiliation: Ustav patologické fyziologie LF MU, Brno. avasku@med.muni.cz
authors.forename: A
authors.initials: A
authors.lastname: Vasků
authors.forename: L
authors.initials: L
authors.lastname: Spinarová
authors.forename: M
authors.initials: M
authors.lastname: Pávková-Goldbergová
authors.forename: J
authors.initials: J
authors.lastname: Spinar
authors.forename: M
authors.initials: M
authors.lastname: Soucek
authors.forename: J
authors.initials: J
authors.lastname: Vítovec
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D000319:Adrenergic beta-Antagonists; D007703:Peptidyl-Dipeptidase A