Serotonin Transporter Genotype, Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 are 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.
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 a class of antidepressants other than SSRI.
Identifying patients who have diminished amounts of the serotonin transporter and, hence, an altered response to SSRI therapeutics
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 inhibitors (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.
For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomics Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Blood samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic blood or marrow transplantation, a pretransplant DNA specimen is recommended for testing.
The test measures only the 5-HTT (LPR) 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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
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 at www.genecards.org/cgi-bin/carddisp?SLC6A4&snpcount=49
3. Serretti A, Kato M, De Ronchi D, Kinoshita T: Meta-analysis of serotonin transporter gene promoter polymorphisms (5-HTTLPR) associated with selective serotonin reuptake inhibitor efficacy in depressed patients. Mol Psych 2007;12:247-257