Methods for selecting medications

• US 20070003931A1
• Filed: 02/20/2004
• Published: 01/04/2007
• Est. Priority Date: 02/20/2003
• Status: Active Grant

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Original Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Inventors: Mrazek, David, Black, John, O'Kane, Dennis
• Granted Patent: US 8,401,801 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6827 for detection of mutation or polymorphism
• 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 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/10 Ontologies; Annotations
• CPC Class Codes: G16H 10/60 for patient-specific data, e.g. for electronic patient records
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

Methods for selecting a medication for a patient are described that include determining the patient'"'"'s genotype for a panel of genes and selecting the medication based on the genotype. Articles of manufacture also are provided that include nucleic acid molecules for detecting alleles of genes encoding drug metabolizing enzymes and genes encoding products involved in neurotransmission.

Claims

1. A method for selecting a psychotropic medication for a patient, said method comprising

(a) providing said patient'"'"'s genotype for a panel of genes, wherein said panel comprises at least three cytochrome P450 genes and a serotonin transporter gene;

and

(b) selecting said psychotropic medication based on said genotype.

2. The method of claim 1, wherein said at least three cytochrome P450 genes encode CYP2D6, 1A2, and 2C19.

3. The method of claim 2, wherein providing said patient'"'"'s genotype comprises determining if said patient comprises the CYP 1A2*1A or 1A2*3 allele, the CYP2C19*1A, 2C19*1B, or 2C19*2A allele, and the CYP2D6*1A, 2D6*2, 2D6*2N, 2D6*3, 2D6*4, 2D6*5, 2D6*6, 2D6*7, 2D6*8, 2D6*10, 2D6*12, or 2D6*17 allele.

4. The method of claim 1, wherein said panel comprises 4 cytochrome P450 genes.

5. The method of claim 1, wherein said 4 cytochrome P450 genes are CYP2D6, 2C19, 3A4, and 1A2.

6. The method of claim 5, wherein providing said patient'"'"'s genotype comprises determining if said patient comprises the CYP2D6*2, 2D6*3, 2D6*4, 2D6*10, or 2D6*17 allele, the CYP2C19*2A, 2C19*2B, 2C19*3, 2C19*4, 2C19*5A, 2C19*5B, 2C19*6, 2C19*7, or 2C19*8 allele, the CYP3A4*1B, 3A4*2, 3A4*5, 3A4*6, 3A4*12, 3A4*13, 3A4*15A, 3A4*17, 3A4*18A allele, and the CYP1A2*1F allele.

7. The method of claim 1, wherein said panel comprises 5 cytochrome P450 genes.

8. The method of claim 7, wherein said 5 cytochrome P450 genes are CYP1A1, 1A2, 2D6, 2C19, and 3A4.

9. The method of claim 8, wherein providing said patient'"'"'s genotype comprises determining if said patient comprises the CYP1A1*1A, 1A1*2, 1A1*3, or 1A1*4 allele, the CYP1A2*1A or 1A2*3 allele, the CYP2C19*1A, 2C19*1B, or 2C19*2A allele, the CYP2D6*1A, 2D6*2, 2D6*2N, 2D6*3, 2D6*4, 2D6*5, 2D6*6, 2D6*7, 2D6*8, 2D6*10, 2D6*12, 2D6*17, or 2D6*35 allele, and the CYP3A4*1A or 3A4*1B allele.

10. The method of claim 1, wherein said panel of genes further comprises a dopamine transporter gene.

11. The method of claim 1, wherein said panel further comprises a plurality of dopamine receptor genes.

12. The method of claim 11, wherein said dopamine receptor genes encode dopamine receptors D1, D2, D3, D4, D5, and D6.

13. The method of claim 1, wherein said panel further comprises a serotonin receptor gene.

14. The method of claim 13, wherein said serotonin receptor gene encodes serotonin receptors 1A, 1B, 1D, 2A, or 2C.

15. The method of claim 13, wherein said serotonin receptor gene encode serotonin receptor 2A.

16. The method of claim 1, wherein said panel further comprises a catechol-O-methyl transferase gene.

17. The method of claim 1, wherein said panel comprises at least 10 cytochrome P450 genes.

18. The method of claim 17, wherein said at least 10 cytochrome P450 genes are CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, and 3A5.

19. The method of claim 18, wherein providing said patient'"'"'s genotype comprises determining if said patient comprises the CYP1A1*1A, 1A1*2, 1A1*3, or 1A1*4 allele;

the 1A2*1A or 1A2*3 allele;

the CYP1B1*1, 1B1*2, 1B1*3, 1B1*4, 1B1*11, 1B1*14, 1B1*18, 1B1*19, 1B1*20, or 1B1*25 allele;

the CYP2A6*1A, 2A6*1B, 2A6*2, or 2A6*5 allele;

the CYP2B6*1, 2B6*2, 2B6*3, 2B6*4, 2B6*5, 2B6*6, or 2B6*7 allele;

the CYP2C8*1A, 2C8*1B, 2C8*1C, 2C8*2, 2C8*3, or 2C8*4 allele;

the CYP2C9*1, 2C9*2, 2C9*3, or 2C9*5 allele;

the CYP2C18*ml or 2C18*m2 allele;

the CYP2C19*1A, 2C19*1B, or 2C19*2A allele;

the CYP2D6*1A, 2D6*2, 2D6*2N, 2D6*3, 2D6*4, 2D6*5, 2D6*6, 2D6*7, 2D6*8, 2D6*10, 2D6*12, 2D6*17, or 2D6*35 allele;

the CYP2E1*1A, 2E1*1C, 2E1*1D, 2E1*2, 2E1*4, 2E1*5, or 2E1*7 allele;

the CYP3A4*1A or 3A4*1B allele; and

the CYP3A5*1A, 3A5*3, 3A5*5, or 3A5*6 allele.

20. The method of claim 1, wherein said panel further comprises a tryptophan hydroxylase gene.

21. The method of claim 1, wherein said psychotropic medication is an antidepressant.

22. The method of claim 1, wherein said psychotropic medication is an antipsychotic agent.

23. The method of claim 1, wherein said psychotropic medication is an antianxiety-sedative agent.

24. The method of claim 1, wherein said psychotropic medication is a mood-stabilizing agent.

25. The method of claim 21, wherein said panel of genes is the CYP2D6, 2C19, 3A4, and 1A2 genes, the serotonin transporter gene, and the serotonin receptor 2A gene.

26. The method of claim 25, wherein selecting said psychotropic medication comprises:

(a) correlating genotype of said cytochrome P450 genes with capacity of each cytochrome P450 enzyme encoded by each said cytochrome P450 gene to metabolize said psychotropic medication; and

(b) correlating genotype of said serotonin transporter gene and said serotonin receptor 2A gene with ability of said patient to respond to said psychotropic medication.

27. An article of manufacture comprising a substrate, said substrate comprising a plurality of discrete regions, wherein each said region comprises a different population of nucleic acid molecules, wherein said different populations of nucleic acid molecules independently comprise nucleic acid molecules for detecting the CYP1A2*1A and 1A2*3 alleles;

the CYP2C19*1A, 2C19*1B, and 2C19*2A alleles;

the CYP2D6*1A, 2D6*2, 2D6*2N, 2D6*3, 2D6*4, 2D6*5, 2D6*6, 2D6*7, 2D6*8, 2D6*10, 2D6*12, 2D6*17, and 2D6*35 alleles;

the CYP3A4*1A and 3A4*1B alleles;

the serotonin receptor 2A C/T, T/T, C/C alleles; and

the 5HTT promoter repeat and exon 2 variable repeat alleles.

28. The article of manufacture of claim 27, wherein said population of nucleic acid molecules further comprises nucleic acid molecules for detecting the CYP1A1*1A, 1A1*2, 1A1*3, and 1A1*4 alleles.

29. The article of manufacture of claim 27, wherein said population of nucleic acid molecules further comprises nucleic acid molecules for detecting the DAT1 40 bp VNTR and 10 repeat alleles.

30. The article of manufacture of claim 27, wherein said population of nucleic acid molecules further comprises nucleic acid molecules for detecting the CYP1B1*1, 1B1*2, 1B1*3, 1B1*4, 1B1*11, 1B1*14, 1B1*18, 1B1*19, 1B1*20, and 1B1*25 alleles, the CYP2A6*1A, 2A6*1B, 2A6*2, and 2A6*5 alleles, the CYP2B6*1, 2B6*2, 2B6*3, 2B6*4, 2B6*5, 2B6*6, and 2B6*7 alleles, the CYP2C8*1A, 2C8*1B, 2C8*1C, 2C8*2, 2C8*3, and 2C8*4 alleles, the CYP2C9*1, 2C9*2, 2C9*3, and 2C9*5 alleles, the CYP2C18*ml and 2C18*m2 alleles, the CYP2C19*1A, 2C19*1B, and 2C19*2A alleles, the CYP2E1*1A, 2E1*1C, 2E1*1D, 2E1*2, 2E1*4, 2E1*5, and 2E1*7 alleles, and the CYP3A5*1A, 3A5*3, 3A5*5, and 3A5*6 alleles.

31. The article of manufacture of claim 27, wherein said population further comprises nucleic acid molecules for detecting the TPH A218C, A779C, G5806T, A6526G, and (CT)_m(CA)_n(CT)_p alleles.

32. A method of building a database for use in selecting a medication for a patient, said method comprising:

(a) receiving, in a computer system, a plurality of genotypes for a panel of genes;

(b) receiving a plurality of medication profiles specified based on the genotypes; and

(c) storing said plurality of genotypes and the medication profiles such that each medication profile is associated with one of the genotypes.

33. The method of claim 32, wherein at least one medication profile identifies a medication.

34. The method of claim 33, wherein the medication is placed in one of multiple categories included in the medication profile.

35. The method of claim 34, wherein each category is selected from the group consisting of:

medications that are safe to use, medications that should be used with caution, medications that should be closely monitored when used, medications that should be avoided, and combinations thereof.

36. The method of claim 33, wherein the medication profile identifies a universe of possible medications for the patient'"'"'s genotype.

37. A computer program product containing executable instructions that when executed cause a processor to perform operations comprising:

(a) receive a plurality of genotypes for a panel of genes;

(b) receive a plurality of medication profiles specified based on the genotypes; and

(c) store the genotypes and the medication profiles such that each medication profile is associated with one of the genotypes.

38. A method of selecting a medication for a patient, the method comprising:

(a) receiving, in a computer system, a patient'"'"'s genotype for a panel of genes;

(b) identifying, in a database comprising a plurality of medication profiles associated with genotypes, a medication profile that is associated with the patient'"'"'s genotype; and

(c) outputting the identified medication profile in response to receiving the patient'"'"'s genotype.

39. The method of claim 38, wherein a user enters the patient'"'"'s genotype in the computer system.

40. The method of claim 38, wherein the patient'"'"'s genotype is received directly from equipment used in determining the patient'"'"'s genotype.

41. The method of claim 38, wherein the identified medication profile includes a ranking of several medications.

42. The method of claim 41, wherein the ranking is based on specific co-factors.

43. The method of claim 41, further comprising adjusting the ranking before outputting the identified medication profile.

44. The method of claim 43, wherein the ranking is adjusted based on receiving a genotypic polymorphism carried by the patient.

45. The method of claim 43, wherein the ranking is adjusted based on receiving a clinical response relating to the patient.

46. The method of claim 45, wherein the clinical response is by a family member of the patient.

47. A computer program product containing executable instructions that when executed cause a processor to perform operations comprising:

(a) receive a patient'"'"'s genotype for a panel of genes;

(b) identify, in a database including a plurality of medication profiles associated with genotypes, a medication profile that is associated with the patient'"'"'s genotype; and

(c) output the identified medication profile in response to receiving the patient'"'"'s genotype.