Tryptophan hydroxylase gene (TPH1) and peripheral tryptophan levels in depression

J Affect Disord. 2008 Jul;109(1-2):209-12. doi: 10.1016/j.jad.2007.11.010. Epub 2008 Feb 21.

Abstract

Background: Genetic variants have been discovered in two genes encoding for tryptophan hydroxylase (TPH)-TPH1 and TPH2. Low tryptophan (TRP) levels are associated with depression and may arise because of stress. Evidence suggests that hypothalamic and peripheral 5HT systems have a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels.

Methods: We examined the association between a polymorphism in intron 7 of TPH1, 218A>C and plasma total TRP levels in 118 patients with major depression.

Results: There was an interaction between 218A>C and gender in determining plasma TRP whereby presence of the 218C allele, in women, was associated with markedly reduced plasma TRP.

Limitations: The study investigated only the TRP1 gene and did not use a haplotype analysis. The results only apply to a population of subjects suffering from major depression.

Conclusions: TPH1 may be associated with the regulation of peripheral tryptophan levels and therefore availability of tryptophan to the brain. This may have relevance to a range of neuropsychiatric conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Primers / genetics
  • Depressive Disorder, Major / blood*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / genetics*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Genotype
  • Homeostasis / physiology
  • Humans
  • Introns / genetics
  • Male
  • Polymorphism, Genetic / genetics
  • Surveys and Questionnaires
  • Tryptophan Hydroxylase / blood*
  • Tryptophan Hydroxylase / genetics*

Substances

  • DNA Primers
  • TPH1 protein, human
  • Tryptophan Hydroxylase