Dopamine Receptor D3 Genotype

CPT CODE:

USEFUL FOR:

Influencing choice of antipsychotics prior to treatment, especially to ascertain if atypical antipsychotics may be used with low risk of tardive dyskinesia.
Identifying those patients receiving antipsychotics who are at increased risk of developing tardive dyskinesias. Individuals with the 25G allele should be monitored closely for signs of tardive dyskinesia if a decision is made to treat with antipsychotics.
Testing may also be considered for individuals who will receive antipsychotic medications, if they are first-degree relatives of patients who have developed tardive dyskinesia.
Assessing potential for effective treatment response with clozapine and olanzapine.

SPECIMEN REQUIRED:

Note:    Multiple drug metabolism genotype tests can be             Performed on a single specimen after a single extraction.             See "Multiple Drug Metabolism Genotype Tests" in             Special Instructions for a list of tests that can be             ordered together.
Draw blood in a lavender-top EDTA tube(s), and send 3 mL ofEDTA whole blood.Note:    1. Bone marrow transplants will interfere with testing.                                   For bone marrow transplant patients, buccal cells                  should be provided from the recipient to obtain                  an accurate genotype.2.  Transfusions will interfere with testing for up to 4 to 6    weeks. DNA obtained from white cells may not provide    useful information for patients who received a recent    transfusion of blood that was not leukocyte-reduced.    Wait 4 to 6 weeks until transfused cells have left the    patient's circulation before drawing the patient's blood    specimen for genotype testing.3.  An "Informed Consent for DNA Testing" (Supply T576)    is available. See Special Instructions for a copy of the    form.

TRANSPORT TEMPERATURE:

Ambient\Refrig OK\Frozen OK

CLINICAL INFORMATION:

The neurotransmitter dopamine acts via dopamine receptors in the central nervous system. Dopamine receptor subtypes D1 through 5 (DRD1-5) are of interest in schizophrenia research because many of the antipsychotic drugs interact with and block 1 or several of these receptors. There has been a strong association between DRD2 receptor blockade and antipsychotic drug dose for typical antipsychotics (eg, haloperidol, chlorpromazine). However, this association has not been maintained for the atypical antipsychotics (eg, clozapine, risperidone). The atypical antipsychotic medications have high binding affinity for the polymorphic DRD3 receptor.  
For DRD3, a single nucleotide change (DRD3 25A->G) results in an amino acid coding polymorphism, Ser9Gly, which is associated with variable response to treatment with atypical antipsychotic medications and predisposition to tardive dyskinesia, a side effect of certain antipsychotic drugs. Worldwide, the frequency of the A (DRD3 25A) and G (DRD3 25G) alleles is nearly equal. However, the allele frequencies are markedly different in different populations (see below) and this may impact the risk of tardive dyskinesia within a given population or cohort following treatment with antipsychotic drugs.
Population Frequencies for DRD3 25A and DRD3 25G Alleles:     Allele frequency      - Global:  G = 48%, A = 52%       - African:  G = 88%, A = 12%      - CEPH*:  G = 15%, A = 85%
*Immortalized cell lines collected for genetic studies and maintained by the Centre d'Etude du Polymorphisme Humaine
Other polymorphisms in the 5' promoter region of DRD3 have also been studied, but results are too preliminary to be used in the management or diagnoses of psychiatric illnesses.
Tardive dyskinesia:The DRD3 25G polymorphism is associated with the presence and severity of typical neuroleptic-induced tardive dyskinesia in schizophrenic patients. Higher mean movement scores were found in patients homozygous for the DRD3 25G allele as compared to both heterozygous and DRD3 25A homozygous patients.(1,2)  The risk for tardive dyskinesia increases with the number of DRD3 25G alleles. Individuals homozygous for the DRD3 25G allele have an odds ratio of 2.8 for developing tardive dyskinesia compared to individuals homozygous for the DRD3 25A allele.(2)
Treatment responses:The DRD3 25G allele has been associated with treatment response to clozapine(3) and olanzapine. Among a group of Chinese patients

CLINICAL INTERPRETATION:

An interpretive report will be provided.

REFERENCE VALUES:

An interpretive report will be provided.