TPH1 is associated with major depressive disorder but not with SSRI/SNRI response in Taiwanese patients

Rationale: Tryptophan hydroxylase 1 (TPH1), which encodes the rate-limiting enzyme tryptophan hydroxylase in the biosynthesis of serotonin, is a candidate gene in the development and treatment response of major depressive disorder (MDD); however, its actual role is uncertain. Objectives: We aimed to compare the allele frequencies of TPH1 in MDD patients and healthy controls in Taiwan, and also to investigate the association between TPH1 A218C and treatment response to either fluoxetine or venlafaxine in a Taiwanese population with MDD. Methods: One hundred five healthy controls and 115 outpatients diagnosed with MDD were recruited and genotyped for the TPH1 218A/C (rs1800532) polymorphism. Patients were randomized into either the fluoxetine or venlafaxine treatment group. The 21-item Hamilton rating scale for depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. Results: The TPH1 218A/C allele frequencies differed significantly between healthy controls and MDD patients in Taiwan, with a higher prevalence of the A allele in the patient group (p = 0.025). The odds ratio of the A allele to the C allele was 0.507 for the subjects with MDD. There was no significant correlation between the percentage change in HAM-D score and either TPH1 218A/C genotype or TPH1 allele frequencies. Conclusions: This study indicated that the TPH1 218A/C genotype and allele frequencies differed between the Taiwanese healthy controls and MDD patients but could not be used to predict treatment outcome in Taiwanese MDD patients. Further research with larger sample sizes is needed to confirm the role of TPH1 218A/C.