title: [Impact of Gly389Arg beta1-adrenoceptor polymorphism on the risk of chronic heart failure, the nature of its course, and on the efficiency of its treatment with carvedilol].
abstract: OBJECTIVE
  To study beta1-adrenoceptor gene (ADRB1) polymorphism on the development and course of chronic heart failure (CHF) and on the efficiency of its treatment with the beta-adrenoblocker carvedilol in patients with coronary heart failure.
  
  
  METHODS
  Two hundred and twenty-six patients (149 males and 77 females; mean age 55.9 +/- 5.8 years) with CHF, who received continuous basic therapy: angiotensin-converting enzyme inhibitors, a diuretic, an aldosterone antagonist, digoxin, and a beta-adrenoblocker, were examined; 68 patients were given for 24 weeks carvedilol (its starting dose was 3.125 mg twice daily with its further adjustment until an individually tolerable dose was achieved). Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 males and 73 females; mean age 55.9 +/- 5.8 years) without signs of cardiovascular disorders, as evidenced by the examination.
  
  
  RESULTS
  In patients with CHF, the Gly allele of the Gly389Arg polymorphic locus of the ADRB1 gene in homozygous state was associated with the high individual risk for CHF, the severity of its clinical manifestations and the nature of its course while carriage of the Arg allele of the Gly39Arg polymorphic locus manifested itself as a protective factor. During long-term carvedilol therapy, CHF patients with the Arg/Arg genotype of the ADRB1 gene were observed to have a more pronounced decrease in the functional class of heart failure, a significant increase in left ventricular ejection, and a decrease in left ventricular end-systolic and end-diastolic sizes as compared with patients with the Gly/Arg genotype.
  
  
  CONCLUSIONS
  There were associations of the polymorphism of ADRB1 gene (the Gly39Arg polymorphic locus) with the development and severity of CHF and with the efficacy of therapy with beta-adrenoblocker carvedilol.
authors.forename: A T
authors.initials: AT
authors.lastname: Tepliakov
authors.forename: S N
authors.initials: SN
authors.lastname: Shilov
authors.forename: E N
authors.initials: EN
authors.lastname: Berezikova
authors.forename: Iu Iu
authors.initials: IuIu
authors.lastname: Torim
authors.forename: A V
authors.initials: AV
authors.lastname: Efremov
authors.forename: I D
authors.initials: ID
authors.lastname: Safronov
authors.forename: S D
authors.initials: SD
authors.lastname: Maianskaia
authors.forename: A A
authors.initials: AA
authors.lastname: Popova
authors.forename: E N
authors.initials: EN
authors.lastname: Voronina
authors.forename: R S
authors.initials: RS
authors.lastname: Karpov
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D000483:Alleles; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077261:Carvedilol; D004247:DNA / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C547787:ADRB1 protein, human; D058668:Adrenergic alpha-1 Receptor Antagonists; D002227:Carbazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D000077261:Carvedilol; D004247:DNA