METHODS AND COMPOSITIONS FOR THE TREATMENT OF PSYCHOTIC DISORDERS THROUGH THE IDENTIFICATION OF THE SULT4A1-1 HAPLOTYPE
Methods and compositions that relate to genetic markers of psychotic disorders, e.g., schizophrenia (SZ), are provided. For example, in certain aspects methods for determinations of a SULT4A1-1 haplotype are described. Furthermore, the invention provides methods and compositions involving treatment of psychotic disorders using the haplotype status.
1 .- 32 . (canceled)
33 . A method for treating a human subject having or suspected of having a psychotic disorder with quetiapine or olanzapine, the method comprising:
a) selecting a subject that has been determined to have a SULT4A1-1 haplotype, wherein the SULT4A1-1 haplotype is defined as a haplotype comprising a C allele at rs763120, a combination of an A allele at rs2285162 and a G allele at rs2285167, or the combination of a T allele at rs2285166 and G allele at rs2285167; and
(b) treating the subject that has the SULT4A1-1 haplotype with quetiapine or olanzapine.
34 . The method of claim 33 , wherein the subject comprises the SULT4A1-1 haplotype and the subject is treated with quetiapine.
35 . The method of claim 33 , wherein the subject comprises the SULT4A1-1 haplotype and the subject is treated with olanzapine.
36 . The method of claim 33 , wherein the psychotic disorder is schizophrenia.
37 . A method for treating a human subject having or suspected of having a psychotic disorder with risperidone, perphenazine, or ziprasidone, the method comprising:
a) selecting a subject that has been determined not to have a SULT4A1-1 haplotype, wherein the SULT4A1-1 haplotype is defined as a haplotype comprising a C allele at rs763120, a combination of an A allele at rs2285162 and a G allele at rs2285167, or the combination of a T allele at rs2285166 and G allele at rs2285167; and
(b) treating the subject that does not have the SULT4A1-1 haplotype with risperidone, perphenazine, or ziprasidone.
38 . The method of claim 37 , wherein the treatment is risperidone.
39 . The method of claim 37 , wherein the treatment is perphenazine.
40 . The method of claim 37 , wherein the treatment is ziprasidone.
41 . The method of claim 37 , wherein the psychotic disorder is schizophrenia.
42 . A method for selecting a pharmacotherapeutic treatment plan for a human subject who is undergoing or is to undergo anti-psychotic treatment, the method comprising: (a) determining the SULT4A1-1 haplotype in a sample, wherein the SULT4A1-1 haplotype is defined as a haplotype comprising a C allele at rs763120, a combination of an A allele at rs2285162 and a G allele at rs2285167, or the combination of a T allele at rs2285166 and G allele at rs2285167, and (b) selecting a pharmacotherapeutic treatment plan comprising olanzapine treatment if the subject comprises the SULT4A1-1 haplotype.
43 . The method of claim 42 , wherein if the subject comprises a SULT4A1-1 haplotype, then the method further comprises treating the subject with olanzapine.
44 . A method for selecting a pharmacotherapeutic treatment plan for a human subject who is undergoing or is to undergo anti-psychotic treatment, the method comprising: (a) determining the SULT4A1-1 haplotype in a sample, wherein the SULT4A1-1 haplotype is defined as a haplotype comprising a C allele at rs763120, a combination of an A allele at rs2285162 and a G allele at rs2285167, or the combination of a T allele at rs2285166 and G allele at rs2285167, and (b) selecting a pharmacotherapeutic treatment plan that does not comprise treatment with olanzapine if the subject does not comprise the SULT4A1-1 haplotype.
45 . The method of claim 44 , wherein if the subject does not comprise a SULT4A1-1 haplotype, then the method further comprises treating the subject with a non-olanzapine anti-psychotic treatment.
46 . The method of claim 45 , wherein the non-olanzapine anti-psychotic treatment comprises risperidone, quetiapine, perphenazine, or ziprasidone.
47 . A method for genotyping a subject who is undergoing or is to undergo anti-psychotic treatment with olanzapine, risperidone, quetiapine, perphenazine, or ziprasidone to determine the presence of a haplotype comprising the steps of: (a) obtaining a biological sample comprising genetic material of the subject, wherein the subject is undergoing or is to undergo anti-psychotic pharmacotherapy; and (b) determining the presence or absence of a SULT4A1-1 haplotype in the biological sample, wherein the SULT4A1-1 haplotype is defined as a haplotype comprising a C allele at rs763120, a combination of an A allele at rs2285162 and a G allele at rs2285167, or the combination of a T allele at rs2285166 and G allele at rs2285167.
48 . The method of claim 47 , further comprising recording the determination of the haplotype in a tangible medium.
49 . The method of claim 48 , wherein the tangible medium comprises a computer-readable disk, a solid state memory device, or an optical storage device.
50 . The method of claim 47 , further comprising extracting DNA from the biological sample.
51 . The method of claim 47 , wherein the genetic material is analyzed by SNP genotyping or sequencing.
52 . The method of claim 47 , further comprising reporting the determination to the subject, a health care payer, a physician, a pharmacist, a pharmacy benefits manager, or an electronic system.
53 . The method of claim 47 , wherein the determining step is carried out through the use of an array or a kit comprising a plurality of primers or probes specific for the SULT4A1-1 haplotype, wherein the SULT4A1-1 haplotype is defined as a haplotype comprising a C allele at rs763120, a combination of an A allele at rs2285162 and a G allele at rs2285167, or the combination of a T allele at rs2285166 and G allele at rs2285167.
54 . A method for treating a human subject having or suspected of having a psychotic disorder with risperidone, quetiapine, ziprasidone, or perphenazine, the method comprising:
a) selecting a subject having a psychotic disorder whose genetic material has been tested and determined to contain the OPRP genetic signature, wherein the OPRP genetic signature is defined as a genotype comprising a homozygous genotype for the T allele at rs11960832 and either a homozygous or heterozygous genotype for the T allele at rs7975477, and
b) treating the subject that was determined not to have the OPRP genetic signature with risperidone, quetiapine, ziprasidone, or perphenazine.
55 . The method of claim 54 , wherein the treatment is risperidone.
56 . The method of claim 54 , wherein the treatment is quetiapine.
57 . The method of claim 54 , wherein the treatment is ziprasidone.
58 . The method of claim 54 , wherein the treatment is perphenazine.
59 . The method of claim 54 , wherein the psychotic disorder is schizophrenia.
60 . A method for treating a human subject having or suspected of having a psychotic disorder with olanzapine, the method comprising:
a) selecting a subject having a psychotic disorder whose genetic material has been tested and determined not to contain the OPRP genetic signature, wherein the OPRP genetic signature is defined as a genotype comprising a homozygous genotype for the T allele at rs11960832 and either a homozygous or heterozygous genotype for the T allele at rs7975477, and
b) treating the subject that was determined not to have the OPRP genetic signature with olanzapine.