Rgs2 genotypes associated with extrapyramidal symptoms induced by antipsychotic medication

Abstract

The present invention identifies genotypes associated with resistance to extrapyramidal symptoms induced by antipsychotic drugs. The present invention further identifies genotypes associated with predisposition to the onset or aggravation of extrapyramidal symptoms induced by antipsychotic drugs and use thereof for assessment of patient populations. Specifically, the present invention relates to particular polymorphisms in the RGS2 gene that are associated with resistance or susceptibility to drug-induced extrapyramidal symptoms.

1 - 20 . (canceled) 
     
     
         21 . A method for assessing a tendency of a subject to develop extrapyramidal symptoms following treatment with an antipsychotic drug, which comprises:
 obtaining a sample comprising genetic material from the subject;   determining, in the genetic material, the nucleotide sequence of the RGS2 gene or a fragment thereof;   identifying in said nucleotide sequence at least one polymorphic site within said RGS2 gene or fragment thereof,   wherein the identity of the at least one polymorphic site is indicative of the tendency to develop at least one extrapyramidal symptom following treatment with antipsychotic drugs.   
     
     
         22 . The method of  claim 21 , wherein the at least one polymorphic site has a reference sequence number on chromosome 1 selected from the group consisting of: rs2179652, rs1933695, rs2746073, rs4606, rs1152746 and rs1819741. 
     
     
         23 . The method of  claim 22 , wherein the presence of at least one of: thymine at rs2179652, guanine at rs1933695, adenine at rs2746073, guanine at rs4606, cytosine at rs1819741 and adenine rs1152746 is indicative of resistance to emergence or aggravation of extrapyramidal symptoms (EPS) following treatment with antipsychotic drugs. 
     
     
         24 . The method of  claim 23 , wherein the presence of at least one of: thymine at rs2179652 and guanine at rs1933695; thymine at rs2179652 and adenine at rs2746073; guanine at rs4606 and adenine at rs2746073; guanine at rs4606 and cytosine at rs1819741; and cytosine at rs1819741 and adenine at rs1152746 is indicative of resistance to emergence or aggravation of EPS following treatment with antipsychotic drugs. 
     
     
         25 . The method of  claim 23 , wherein the presence of guanine at nucleotides rs1933695 and rs4606, thymine at nucleotide rs2179652, cytosine at nucleotide rs1819741 and adenine at nucleotide rs1152746 is indicative of resistance to emergence or aggravation of EPS following treatment with antipsychotic drugs. 
     
     
         26 . The method of  claim 23 , wherein the presence of guanine at rs4606, thymine at rs2179652, cytosine at rs1819741 and adenine at rs1152746 is indicative of resistance to emergence or aggravation of EPS following treatment with antipsychotic drugs. 
     
     
         27 . The method according to  claim 22 , wherein the presence of at least one of: thymine at rs2746073, thymine at rs1819741, cytosine at rs2179652, cytosine at rs4606 and guanine at rs1152746, is indicative of susceptibility to emergence or aggravation of extrapyramidal symptoms following treatment with an antipsychotic drug. 
     
     
         28 . The method according to  claim 27 , wherein the presence of at least one of: thymine at rs1819741 and guanine at rs1152746; thymine at rs1819741 and cytosine at rs4606; thymine at rs1819741 and guanine at rs1933695; thymine at rs1819741 and cytosine at rs2179652; thymine at rs2746073 and cytosine at rs2179652; thymine at rs2746073 and cytosine at rs4606; and cytosine at rs2179652 and guanine at rs1933695, is indicative of susceptibility to emergence or aggravation of EPS following treatment with an antipsychotic drug. 
     
     
         29 . The method according to  claim 27 , wherein the presence of guanine at rs1933695 and rs1152746, cytosine at rs2179652 and rs4606 and thymine at rs1819741, is indicative of susceptibility to emergence or aggravation of EPS following treatment with an antipsychotic drug. 
     
     
         30 . The method of  claim 21 , wherein the sample is obtained from a biological specimen selected from the group consisting of: blood, saliva, urine, sweat, buccal material, skin and hair. 
     
     
         31 . The method of  claim 21 , wherein identifying the at least one polymorphic site is attained by a technique selected from the group consisting of: terminator sequencing, restriction digestion, allele-specific polymerase reaction, single-stranded conformational polymorphism analysis, genetic bit analysis, temperature gradient gel electrophoresis ligase chain reaction and ligase/polymerase genetic bit analysis. 
     
     
         32 . The method of  claim 21 , wherein the polymorphic site is identified by employing nucleotides with a detectable characteristic selected from the group consisting of inherent mass, electric charge, electric spin, mass tag, radioactive isotope type bioluminescent molecule, chemiluminescent molecule, nucleic acid molecule, hapten molecule, protein molecule, light scattering/phase shifting molecule and fluorescent molecule. 
     
     
         33 . The method of  claim 21 , wherein the subject is psychotic. 
     
     
         34 . The method of  claim 21 , wherein said method is performed prior to initiation of treatment with a composition comprising an antipsychotic drug. 
     
     
         35 . The method of  claim 34 , wherein the antipsychotic drug is selected from the group consisting of: zuclopenthixol, haloperidol, perphenazine, clotiapine, fluphenazine, flupenthixol, levomepromazine, chlorpromazine, sulpiride, penfluridol, pimozide, molindone, thiothixene, thioridazine, trifluoperazine, loxapine, prochlorperazine and combinations thereof. 
     
     
         36 . The method of  claim 34 , wherein the antipsychotic drug further comprises at least one atypical antipsychotic drug. 
     
     
         37 . The method of  claim 36 , wherein the at least one atypical antipsychotic drug is risperidone. 
     
     
         38 . The method of  claim 21 , further comprising repeating the determining and identifying steps. 
     
     
         39 . The method of  claim 21 , further comprising amplifying said nucleotide sequence of the RGS2 gene or a fragment thereof prior to the identifying step.