|Values are valid only on day of printing.|
Qualifying participants for clinical trials
Evaluating patients who have failed therapy with selective serotonin reuptake inhibitors (SSRIs)
Evaluating patients with treatment-resistant depression
Predicting response time to improvement with SSRIs
Identifying patients who might respond favorably to nonselective antidepressants
Identifying patients who have diminished amounts of the serotonin transporter and, hence, an altered response to SSRI therapeutics
Genotyping patients who prefer not to have venipuncture done
Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter. The serotonin transporter (5-HTT) modulates neurotransmission by facilitating removal of serotonin from the synapse of serotonergic neurons, resulting in serotonin reuptake into the presynaptic terminus. Other designations for 5-HTT are SLC6A4 (solute carrier family 6 [neurotransmitter transporter, serotonin], member 4), hSERT, OCD1, SERT, sodium-dependent serotonin transporter, and 5-HT transporter.
Selective serotonin reuptake inhibitors (SSRIs) block the action of the serotonin transporter and are used to treat depression and other neuropsychiatric disorders. Examples of SSRIs include fluoxetine (Prozac), fluvoxamine (Luvox), escitalopram oxalate (Lexapro), sertraline (Zoloft), citalopram (Celexa), and paroxetine (Paxil, Paxil CR).
The 5-HTT gene is located at 17q11.1-q12 and is composed of 14 exons spanning 31 kb. A 44-base pair promoter insertion/deletion polymorphism called LPR, or linked polymorphic region, produces alleles described as long or short. The short allele is dominant and results in decreased concentration of the transporter protein and a poorer response to stressful events. While individuals homozygous for the long allele (l/l) may demonstrate response to SSRI therapy in 3 to 4 weeks, individuals with the short allele (l/s or s/s) may respond to SSRI therapy more slowly, taking up to 12 weeks.
An interpretive report will be provided.
The normal (wildtype) allele yields a long product (l/l). The variant is short/short (s/s). Heterozygotes have a l/s genotype.
Individuals homozygous for the long allele (l/l) may respond more rapidly to selective serotonin reuptake inhibitor (SSRI) therapy.
Individuals homozygous for the short allele (s/s) may respond more slowly to SSRI therapy and may benefit from a longer trial before considering switching to another antidepressant. Even 1 copy of the short allele (heterozygous) decreases the amount of the transporter protein present, increasing the time to response.
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.
The test measures only the 5-hydroxytryptamine transporter (5-HTT)(linked polymorphic region) polymorphism and will not indicate the presence of any other polymorphism. A mutation occurring at the site of PCR primer annealing could lead to a heterozygote being incorrectly labeled as a homozygote.
1. Lesch KP, Gutnecht L: Pharmacogenetics of the serotonin transporter. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:1062-1073
2. Genecard at NCBI for 5-HTT. XenneX, Inc. 2005 October 18; Retrieved 1/06; Available from URL: http://www.genecards.org/cgi-bin/carddisp?SLC6A4&snpcount=49