Serotonin Transporter Genotyping (5-HTT or SLC6A4)

Test Code

CPT Code

Whole blood or buccal swabs

5 mL of whole blood or four buccal swabs

Minimum Volume
3 mL of whole blood or four buccal swabs

Lavender-stopper (EDTA) tube or paper envelope for dried buccal swabs

Storage Instructions
Maintain at room temperature or refrigerate

Cause for Rejection
Hemolyzed specimen; quantity not sufficient

General Purpose and Use
The 5-HTTLPR (5-hydroxytryptamine transporter linked polymorphic region) polymorphism is a 44-bp insertion/deletion in the promoter region of the serotonin transporter gene, 5-HTT or SLC6A4. The two most frequent alleles are defined by their length: the (L)ong allele, and the (S)hort allele characterized by a 43-bp deletion.

The S allele results in 50% less expression of the active transporter protein as compared to the Long form. Presence of the short form may increase the time to therapeutic response with selective serotonin antidepressant therapy and may also affect efficacy. The short form has also been associated increased risk of side effects, and the nature and extent of depressive symptoms experienced.

The Long allele of 5-HTTLPR contains an A>G polymorphism which generates a restriction site that may be detected by restriction fragment length polymorphism analysis. Presence of the G allele is thought to result in a phenotype similar to that of the Short 5-HTTLPR allele. Therefore, the presence of the LG allele is associated with the same risks as that of the Short allele.

Other variants of the serotonin transporter gene that are not detected in this assay may influence drug response. Serotonin concentration and action are also influenced by concomitant medications and various disease states. All factors should be considered as part of the overall patient management strategy.

Polymerase chain reaction and restriction fragment length polymorphism analysis with agarose gel electrophoresis size determination.

Informed Consent
Informed consent for SLC6A4 5-HTTLPR LA/LG genotyping is required for patients residing in New York State. The informed consent document is required to be completed along with the test requisition form for these patients.

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