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Test ID: DRD3 Dopamine Receptor D3 Genotype

Reporting Name

DRD3 Genotype

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, olanzapine, and risperidone

Specimen Type

Whole Blood EDTA


Specimen Required


Multiple whole blood EDTA genotype tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.

 

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL


Specimen Minimum Volume

0.3 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood EDTA Ambient (preferred)
  Refrigerated 

Reference Values

An interpretive report will be provided.

Day(s) and Time(s) Performed

Wednesday; 8 a.m.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81479 -Unlisted molecular pathology procedure

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DRD3 DRD3 Genotype In Process

 

Result ID Test Result Name Result LOINC Value
81776 DRD3 Genotype In Process
30474 Reviewed by No LOINC Needed

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

 - European: G=35%, A=65%

 - African American: G=70%, A=30%

 - Han Chinese Beijing: G=37%, A=63%

 - Japanese: G=24%, A=76%

 

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 with schizophrenia treated with risperidone, patients homozygous for the DRD3 25A allele had a better response, as measured by improved scores on the Positive and Negative Symptom Scale (PANSS), a questionnaire used to evaluate symptoms associated with schizophrenia, compared to patients homozygous for the DRD3 25G allele.(4) These improved responses included decreased social and emotional withdrawal, improved abstract thinking, and increased spontaneity and flow of conversation. A better response was observed in the heterozygous state (DRD3 25AG) compared to the homozygous groups (DRD3 25GG, P=0.05; DRD3 25AA P=0.06) in another study of patients receiving a variety of typical and atypical antipsychotics.(5)

Interpretation

An interpretive report will be provided.

Clinical Reference

1. Lerer B, Segman RH, Fangerau H, et al: Pharmacogenetics of tardive dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism. Neuropsychopharmacology 2002;27:105-119

2. de Leon J, Susce MT, Pan RM, et al: Polymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness. J Clin Psychopharmacol 2005;25:448-456

3. Scharfetter J, Chaudry HR, Hornik K, et al: Dopamine D3 receptor gene polymorphism and response to clozapine in schizophrenic Pakistani patients. Eur Neuropsychopharmacol 1999;10(1):17-20

4. Lane HY, Hsu SK, Liu YC, et al: Dopamine D3 receptor Ser9Gly polymorphism and risperidone response. J Clin Psychopharmacol 2005;25(1):6-11

5. Reynolds GP, Yao Z, Zhang X, et al: Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response. Eur Neuropsychopharmacol 2005;15:143-151

Analytic Time

2 days

Method Name

Polymerase Chain Reaction (PCR) Amplification with Allele-Specific Primer Extension (ASPE)

Forms

New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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