B-Blocker Pharmacogenetics in Heart Failure
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsJulie Johnson, Steven Terra
Life of this patent
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Abstract
Polymorphisms in the beta-1 adrenergic receptor that (1) affect tolerability to beta-blocker treatment or (2) influence responsiveness to beta-blocker treatment are disclosed. Additionally, methods of predicting that an individual would obtain clinical improvement in left ventricular function as a result of β-blocker therapy or identifying at least one individual that would obtain a clinical improvement in left ventricular function as a result of β-blocker therapy are provided. Methods of treating patients characterized by such polymorphisms are also illustrated.
Claims20
A method of selecting at least one individual for treatment with β-blockers for the improvement of left ventricular ejection fraction response comprising:
- a) genotyping the β1 adrenergic receptor (β1AR) and the α2C adrenergic receptor (ADRA2C) gene of at least one individual;
- b) determining whether the genotype of the β1AR gene of said at least one individual is Arg389Arg and the genotype of the ADRA2C gene is DEL;
- and
- c) selecting said at least one individual for treatment with β-blockers if said exhibits the ARG389ARG and DEL genotype.
A method of predicting that an individual would obtain clinical improvement in left ventricular function as a result of β-blocker therapy or identifying at least one individual that would obtain a clinical improvement in left ventricular function as a result of β-blocker therapy comprising:
- a) genotyping the β1 adrenergic receptor (β1AR) gene and the α2C adrenergic receptor (ADRA2C) gene of at least one individual;
- b) determining whether the genotype of the β1AR gene of said at least one individual is Arg389Arg and the genotype of the ADRA2C gene is DEL;
- and
- c) identifying or predicting that an individual exhibiting the ARG389ARG and DEL genotype is expected obtain a clinical improvement in left ventricular function as a result of β-blocker therapy.
A method of treating at least one individual having impaired left ventricular function comprising:
- a) genotyping the β1 adrenergic receptor (β1AR) gene and the α2C adrenergic receptor (ADRA2C) gene of at least one individual;
- b) determining whether the genotype of the β1AR gene of said at least one individual is Arg389Arg and the genotype of the ADRA2C gene is DEL;
- and
- c) administering a β-blocker medication to said individual if the genotype of the β1AR gene of said at least one individual is Arg389Arg and the genotype of the ADRA2C gene is DEL.
A method of treating an individual, comprising providing, on the basis of β1 adrenergic receptor (β1AR) genotype, an appropriate degree of monitoring during initiation of beta-blockade, wherein individuals having a Gly49 carrier genotype or an Arg 389 homozygous genotype are monitored less closely and wherein patients having a Ser49 homozygous genotype or Gly389 carrier genotype are monitored more closely.
A method of predicting a need for increased monitoring or treatment in a heart failure patient comprising genotyping the β1 adrenergic receptor (β1AR) and identifying the codons at positions 49 and 389 of said patient, wherein the presence of a Ser49Ser homozygous genotype or Arg389Gly variant is associated with a requirement for increased monitoring of said heart failure patient during titration with a β-blocker medication or an increase in concomitant heart failure therapy as compared to a patient having a Ser49Gly genotype or an Arg389Arg genotype.
A method of predicting an individual's tolerability to beta-blocker treatment, comprising determining the genotype of said individual at codon 49 or codon 389 of the gene encoding the β1 adrenergic receptor (β1AR).
A method of predicting an individual's responsiveness to beta-blocker treatment, comprising determining the genotype of said individual at codon 49 or codon 389 of the gene encoding the β1 adrenergic receptor (β1AR).
A method of treating an individual, comprising providing, on the basis of β1 adrenergic receptor (β1AR) genotype, an appropriate therapeutic agent, wherein beta blocker medications are prescribed preferentially or in greater proportion to an individual having a Gly49 carrier genotype or an Arg 389 homozygous genotype and wherein patients having a Ser49 homozygous genotype or Gly389 carrier genotype are preferentially or in greater proportion prescribed alternative non-beta blocker therapeutics.
Dependencies are inferred from the claim text.