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.
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.