TPH2 genetics (tryptophan hydroxylase 2)

TPH2 (tryptophan hydroxylase 2) is the enzyme that nerve cells in the brain use to make serotonin. It carries out the first and rate-limiting step: the amino acid tryptophan is turned into 5-hydroxytryptophan (5-HTP). The TPH2 gene is examined for known variants; which ones were determined is stated in the report. The sample is EDTA blood; as a genetic test, written consent is required. TPH2 is part of the “Depression genetics” analysis. Unlike measuring serotonin in blood or urine, which comes mainly from the gut, the genetic test does not capture a messenger but an inherited property of the enzyme.

What TPH2 does in the body

Humans have two tryptophan hydroxylases. TPH1 works mainly in the enterochromaffin cells of the gut lining, which produce most of the body's serotonin, and in the pineal gland. TPH2 works in the raphe nuclei of the brainstem, from which serotonergic nerve pathways reach almost the entire brain, and in the nerve cells of the gut wall. Because serotonin cannot cross the blood-brain barrier, the brain depends on its own production via TPH2. The enzyme needs iron, oxygen and tetrahydrobiopterin (BH4); in the second step, a decarboxylase with vitamin B6 converts 5-HTP into serotonin. How much is produced also depends on how much tryptophan reaches the brain.

What does a TPH2 variant mean for serotonin production?

The most frequently studied variants lie in the gene's control region, such as G-703T (rs4570625). They do not change the enzyme itself but possibly how strongly the gene is read; laboratory studies have produced differing results on this. In addition, rare variants have been described that change the enzyme itself and markedly lower its activity in the laboratory; they have been found in only very few people. Lower TPH2 output would mean that serotonergic nerve cells replenish less serotonin and have less available for release. Whether the common variants cause measurably less serotonin in the human brain has not been clarified.

What can be read from the TPH2 genotype?

Links between TPH2 variants and mood, stress processing or response to medicines have been examined in studies; the findings are inconsistent, and individual results could not be confirmed in large genetic studies. The genotype does not allow any statement about personality or a disease. It describes an inherited property of serotonin production in the brain. How much tryptophan is available, how much of it flows into the kynurenine pathway and how much serotonin is produced is shown by measurements of tryptophan, kynurenine and serotonin – they have their own pages.

The interpretation is given in your report.