Polymorphisms in the PDE3A gene

• US 9,512,481 B2
• Filed: 09/13/2010
• Issued: 12/06/2016
• Est. Priority Date: 09/11/2009
• Status: Active Grant

• Current Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Sucharov, Carmen, Bristow, Michael, Taylor, Matthew, Slavov, Dobromir
• Primary Examiner(s): Shen, Wu-Cheng Winston
• Assistant Examiner(s): Rodriguez, Rayna B
• Application Number:
  US13/395,311
• Publication Number:
  US 20130203827A1
• Time in Patent Office: 2,276 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Embodiments of the invention are directed to identifying or treating a patient that would benefit from phosphodiesterase inhibitor therapy.

Claims

1. A method for treating a human patient with heart failure comprising treating the patient with an effective amount of a PDE3A inhibitor after the patient is determined to be homozygous for an insertion of an ectotropic viral integration site-1 (Evi-1) binding site in the phosphodiesterase type 3A (PDE3A) gene promoter, wherein the Evi-1 binding site insertion is 85% identical to SEQ ID NO:

2 and is located within 2000 nucleotides 5′

of the PDE3A gene transcriptional initiation site and wherein the PDE3A inhibitor is amrinone, cilostazol, milrinone, quazinone, siguazodan, trequinsin, or enoximone.

2. The method of claim 1, wherein the PDE3A inhibitor is enoximone.

3. The method of claim 1, wherein the PDE3A inhibitor is administered at the dose of 15 mg to 100 mg.

4. The method of claim 1, wherein the PDE3A inhibitor is administered 1, 2, 3 or more times a day.

5. The method of claim 1, wherein the PDE3A inhibitor is administered 1, 2, 3, 4, 5 or more times a week.

6. The method of claim 1, wherein the insertion is 29 nucleotides in length.

7. The method of claim 1, wherein the insertion is identical to SEQ ID NO:

2.

8. A method for treating a patient with heart failure comprising treating the patient with an effective amount of a enoximone after the patient is determined to be homozygous for an insertion having a sequence identical to SEQ ID NO:

2 and located within 2000 nucleotides 5′

of the PDE3A gene transcriptional initiation site.

9. The method of claim 8, wherein the patient is determined to be homozygous for an Evi-1 insertion based on analyzing a sample of the patient by performing nucleic acid sequencing, restriction digestion, allele-specific nucleic acid amplification, single-stranded conformational polymorphism analysis, or allele specific hybridization analysis.

10. The method of claim 8, wherein enoximone is administered at the dose of 15 mg to 100 mg.

11. The method of claim 8, wherein enoximone is administered 1, 2, 3 or more times a day.

12. The method of claim 8, wherein enoximone is administered 1, 2, 3, 4, 5 or more times a week.