Dopamine Receptor D3 Genotype, Saliva
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR)/Amplification with Allele-Specific Primer Extension (ASPE)
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
DRD3 Genotype, Saliva
Dopamine D3 Receptor
Dopamine Receptor Type 3
Dopamine D3 Receptor
Dopamine Receptor Type 3
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple saliva genotype tests can be performed on a single specimen after a single extraction. See Multiple Saliva Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Oragene DNA Self-Collection Kit (Supply T651)
Specimen Volume: Full tube
1. Fill tube to line.
2. Send specimen in original container per kit instructions.
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 (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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:
- 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.
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)
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)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test does not detect polymorphisms other than the A->G polymorphism that causes the Ser9Gly amino acid change. Historically, that polymorphism was designated at position 25 of the cDNA. However, more recent work designates the A->G polymorphism leading to the Ser9Gly change at position 456 of the cDNA.
In patients who have received a recent blood transfusion or undergone an allogeneic hematopoietic cell or bone marrow transplantation, genotyping using DNA obtained from leukocytes may not provide useful information. For patients who have received a transfusion, wait 4 to 6 weeks until transfused cells have left the circulation before testing. For patients who have undergone allogeneic hematopoietic cell or bone marrow transplantation, DNA must be extracted from other cell types, such as buccal cells, that are collected in a manner to avoid blood contamination. Please contact Mayo Medical Laboratories should this be a concern.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from saliva. Direct polymorphism analysis for DRD3 is performed after PCR and allele specific primer extension with Luminex Molecular Diagnostics' proprietary Universal Tag sorting system on the Luminex 100 xMAP platform. A genotype is assigned based on the allele-specific fluorescent signals that are detected. (Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Wednesday; 8 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479 -Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|32978||DRD3 Genotype||In Process|