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Test ID DRD4O Dopamine Receptor D4 Genotype (DRD4), Saliva

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

 

Genotyping patients who prefer not to have venipuncture done

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

DRD4 Genotype, Saliva

Specimen Type

Saliva

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: fees apply)

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

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Saliva Ambient

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 (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.

 

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. 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

Note that in patients who have received heterologous blood transfusions before a saliva sample was acquired, the saliva samples may contain donor DNA. Return to recipient genotype usually occurs after 6 weeks. Similarly, saliva samples obtained from patients after allogeneic blood or marrow transplantation can contain donor DNA. In both cases, this may result in genotyping results that reflect the genotype of the recipient, the donor, or a blend of the donor and recipient. Results obtained under these circumstances may not accurately reflect the recipient’s genotype.

 

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

 

The 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