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Test ID DRD4 Dopamine Receptor D4 Genotype (DRD4), Blood

Useful For

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

Method Name

Polymerase Chain Reaction (PCR) Followed by Sizing Analysis
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)

Reporting Name

Dopamine Receptor D4 Genotype, B

Specimen Type

Whole Blood EDTA

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

Forms: New York Clients-Informed consent is required. Please document on 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

0.3 mL

Specimen Stability Information

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

Clinical Information

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 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 the table. 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.

 

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 (ADHD):

Several studies have found associations between the DRD4 7R allele and 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. The effect of other repeat numbers has not been defined to date and, if other alleles than the 4R and 7R are present, caution should be exercised in using methylphenidate to treat ADHD because the impact of these alleles on treatment response is not known.

 

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

An interpretive report will be provided.

Cautions

Patients who have received a heterologous blood transfusion within the preceding 6 weeks, or who have received an allogeneic blood or marrow transplant, can have inaccurate genetic test results due to presence of donor DNA.  

 

This test does not detect polymorphisms other than the exon 3 variable number tandem repeat (VNTR).

 

The dopamine receptor D4 gene (DRD4) VNTR alleles are not correlated with the variability of antipsychotic drug response; this test should not be ordered for that purpose.

Day(s) Performed

Friday; 8 a.m.

Report Available

1 day

Performing Laboratory

Mayo Medical Laboratories in Rochester

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

NY State Approved

Conditional