Methods and compositions for the treatment of psychotic disorders through the identification of the sult4a1-1 haplotype

Abstract

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.