Test ID: DRD4O
Dopamine Receptor D4 Genotype (DRD4), Saliva
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Influencing the target dose of methylphenidate treatment for patients with attention deficit/hyperactivity disorder
Determining possible cause for poor response to methylphenidate in treated patients with attention deficit/hyperactivity disorder
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
Method Name A short description of the method used to perform the test
Polymerase Chain Reaction (PCR) Followed by Sizing Analysis
(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
Aliases Lists additional common names for a test, as an aid in searching
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
Collection Instructions:
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.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Saliva | Ambient | |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The dopamine receptor D4 gene (DRD4) is located near the telomeric region of chromosome 11q and is a highly variable gene. A 48-base pair (bp) variable number tandem repeat (VNTR) polymorphism in exon 3 of DRD4, which ranges from 2 to 11 repeats, creates a 32- to 176-amino acid variation in the third intracellular loop on the dopamine receptor. The frequency of these alleles is shown in Table 1. The DRD4 7-repeat allele (7R) has functional consequences and is associated with lower affinity for dopamine receptor agonists and reduced signal transduction (eg, cAMP levels) compared to the more common DRD4 4-repeat allele (4R). The effect of other copy number repeats is not as well defined to date, however, and VNTRs with 6 or fewer repeats are grouped as 4R and those with 7 or more repeats as 7R.
Table 1: Frequency of alleles with various DRD4 exon 3 48-bp repeats
| Allele/Number of Repeats (R) | Allelic Frequency (%) |
| 2R | 8.8 |
| 3R | 2.4 |
| 4R | 65.1 |
| 5R | 1.6 |
| 6R | 2.2 |
| 7R | 19.2 |
| 8R | 0.6 |
| 9R | <0.1 |
| 10R | <0.1 |
| 11R | <0.1 |
The DRD4 protein is expressed in a number of brain regions, with higher levels of expression in the prefrontal cortex, where animal models suggest that it inhibits neuronal firing.
Attention Deficit/Hyperactivity Disorder:
Several studies have found associations between the DRD4 7R allele and attention deficit/hyperactivity disorder (ADHD).(1,2) Similarly, a long form (240-bp variant) of a DRD4 promotor repeat polymorphism is associated with ADHD susceptibility, possibly due to linkage disequilibrium with the DRD4 7R allele.(3)
Pharmacogenetics:
Several studies demonstrate that the presence of the DRD4 7R allele, alone or in combination with the SLC6A4 long/long promotor polymorphism of the serotonin transporter, is associated with lower responsiveness of ADHD to methylphenidate (eg, Ritalin, Concerta), the main treatment for ADHD.(4) Methylphenidate dosage may have to be increased to effectively treat individuals with the DRD4 7R allele. Attempts to find an association between DRD4 genotype and the variability of response to antipsychotic drugs, especially clozapine, have been largely unsuccessful or have yielded conflicting results.
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.
Interpretation Provides information to assist in interpretation of the test results
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 exon 3 VNTR.
The DRD4 VNTR alleles are not correlated with the variability of antipsychotic drug response; this test should not be ordered for that purpose.
In patients who have had a recent transfusion, genotyping using DNA obtained from white cells may not provide useful information; wait 4 to 6 weeks until transfused cells have left the circulation.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Ding Y, Chi H-C, Grady D, et al: Evidence of positive selection acting at the human dopamine receptor D4 gene locus. PNAS 2002;99(1):309-314
2. Online Inheritance in Man. Viewed on 4/01/2008 at URL: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=126452
3. Kustanovich V, Ishii J, Crawford L, et al: Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5. Mol Psychiatry 2004;9(7):711-717
4. Hamarman S, Fossella J, Ulger C, et al: Dopamine receptor 4 (DRD4) 7-repeat allele predicts methylphenidate dose response in children with attention deficit hyperactivity disorder: a pharmacogenetic study. J Child & Adolesc Psychopharmacol 2004;14(4):564-574
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from saliva. Genotyping for DRD4 polymorphisms utilizes PCR followed by a size assay of the amplicon performed on the Agilent Bioanalyzer 2100. Each sample is amplified in 1 PCR reaction. An aliquot of the PCR product is sized using an Agilent chip. Alleles are detected by comparing the sizes observed in the assay with known standards. Ambiguous assays are directly sequenced reflexively. Genotypes are assigned based upon the alleles 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.
Friday; 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.
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 |
|---|---|---|
| 32982 | 48 BP Repeat Genotype | In Process |
| 32983 | Reviewed by | N/A |
| 32984 | Interpretation | 69047-9 |
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