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

Reporting Name

Dopamine Receptor D4 Genotype, B

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

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


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

Friday; 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 -Unlisted molecular pathology procedure

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DRD4 Dopamine Receptor D4 Genotype, B In Process

 

Result ID Test Result Name Result LOINC Value
89096 48 BP Repeat Genotype 82939-0
29115 Interpretation 69047-9
29116 Reviewed by No LOINC Needed

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.

Interpretation

An interpretive report will be provided.

Clinical Reference

1. Ding Y, Chi H-C, Grady D, et al: Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proc Natl Acad Sci U S A 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

Analytic Time

1 day

Method Name

Polymerase Chain Reaction (PCR) Followed by Sizing Analysis

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 (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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