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Test ID: DRD3 Dopamine Receptor D3 Genotype, Whole Blood

Reporting Name

DRD3 Genotype

Useful For

Predicting the likelihood of change in negative symptoms among patients with schizophrenia during risperidone therapy

 

Predicting the response of children with autism to risperidone therapy

 

Predicting the likelihood of gastrointestinal symptoms among patients with Parkinson disease treated with levodopa

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

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.


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

Varies; 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

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 82939-0
30474 Reviewed by 18771-6

Clinical Information

The neurotransmitter dopamine acts via dopamine receptors in the central nervous system. The atypical antipsychotic medications have high binding affinity for the polymorphic DRD3 receptor. The c.25G>A (rs6280) single nucleotide change within the DRD3 gene results in a change in the ninth encoded amino acid from glycine to serine (p.Gly9Ser); however, this variant is often referred to in the literature as the Ser9Gly polymorphism.. This variant has been studied for associations with response to treatment with atypical antipsychotic medications of patients with schizophrenia, predisposition to schizophrenia, and risk for tardive dyskinesia. In addition, several more recent studies have evaluated the relationship between this variant and response to risperidone among patients with autism.

 

While early studies suggested that this variant may be associated with response to clozapine among patients with treatment resistant schizophrenia, a recent systematic review found that among 9 studies involving this variant only the initial 2 studies reported that the Gly variant was associated with a favorable response to clozapine, while all 7 subsequent studies (including the 2 with the largest sample size) found nonsignificant results.(1) Another recent systematic review and meta-analysis focused on risperidone treatment in patients with schizophrenia. Among 12 studies, this group found that although the Ser9Gly DRD3 variant was not associated with improvement in the positive and negative symptom scale (PANSS) score, it may be related to a change in negative symptoms.(2) Finally, another updated meta-analysis involving 73 studies for a total of 10,634 patients with schizophrenia and 11,258 controls found no association between the DRD3 Ser9Gly polymorphism and risk of schizophrenia.(3)

 

A study involving 56 children with autism found that carriers of the Gly allele showed significantly better response to risperidone as compared with carriers of the Ser allele; however, this was a single study that has not yet been replicated.(4)

 

In a study of 217 patients with Parkinson disease who were taking levodopa therapy, both the DRD3 rs6280 Ser/Ser genotype and the DRD2 rs1799732 Ins/Ins genotype were found to be independent predictors of levodopa-induced gastrointestinal symptoms.(5) Although this finding is of interest, it has not been replicated in a second cohort to date.

 

The DRD3 c.25A>G, p.Gly9Ser polymorphism has been the most studied polymorphism in tardive dyskinesia (TD). Although early reports identified significant associations with the G allele and risk for TD and the initial meta-analysis also supported these findings.(6) The significance has decreased in more recent literature and meta-analyses.(7) Other variants in this gene have not been well studied.(5)

Interpretation

An interpretive report will be provided.

Clinical Reference

1. Samanaite R, Gillespie A, Sendt K, et al: Biological Predictors of Clozapine Response: A Systematic Review. Front Psychiatry 2018;9:327

2. Ma L, Zhang X, Xiang Q, et al: Association between dopamine receptor gene polymorphisms and effects of risperidone treatment: A systematic review and meta-analysis. Basic Clin Pharmacol Toxicol 2018 Aug 13. doi: 10.1111/bcpt.13111. Epub ahead of print

3. Qi XL, Xuan JF, Xing JX, et al: No association between dopamine D3 receptor gene Ser9Gly polymorphism (rs6280) and risk of schizophrenia: an updated meta-analysis. Neuropsychiatr Dis Treat 2017;13:2855-2865

4. Firouzabadi N, Nazariat A, Zomorrodian K: DRD3 Ser9Gly Polymorphism and Its Influence on Risperidone Response in Autistic Children. J Pharm Pharm Sci 2017;20(1):445-452

5. Rieck M, Schumacher-Schuh AF, Altmann V, et al: Association between DRD2 and DRD3 gene polymorphisms and gastrointestinal symptoms induced by levodopa therapy in Parkinson’s disease. Pharmacogenomics J 2018;18:196-200

6. 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

7. Zai CC, Maes MS, Tiwari AK, et al: Genetics of Tardive Dyskinesia: Promising Leads and Ways Forward. J Neurol Sci 2018;15(389):28-34

Analytic Time

2 days

Method Name

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

Forms

1. 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.

2. If not ordering electronically, complete, print, and send a Pharmacogenomics Test Request Form (T797) with the specimen (https://www.mayomedicallaboratories.com/it-mmfiles/pharmacogenomics-test-request-form-mc0767-15.pdf)

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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