Common genetic variations in TPH1/TPH2 genes are not associated with schizophrenia in Japanese population

Abstract

Alteration of serotonin transmission in the brain of patients with schizophrenia has been reported in postmortem brain studies, cerebrospinal fluid studies, and pharmacological challenges. Although a genetic association of tryptophan hydroxylase isoform 1 (TPH1), the rate-limiting enzyme in serotonin synthesis, with schizophrenia has been suggested by recent systematic meta-analyses, the newly identified neuronal isoform TPH2 is more relevant to the central nervous system and the association of TPH2 gene with schizophrenia has been much less explored. We, therefore, explored the association of TPH2 gene with schizophrenia using a case-control study of 720 Japanese populations and also tried to replicate the association of the TPH1 rs1800532 (A218C) single nucleotide polymorphism (SNP) with schizophrenia. We selected 15 tagging SNPs in the TPH2 gene. We found no significant differences in genotypic distributions (uncorrected P=0.18-0.98) or allelic frequencies (uncorrected P=0.18-0.98) of the 15 SNPs between the schizophrenia and control groups. Haplotypes constructed with these SNPs were also not associated with schizophrenia (uncorrected P=0.12-0.97). The genotypic and allelic distribution of the TPH1 rs1800532 SNP was also not different between the case and control groups in our samples. In addition, a subsequent meta-analysis including our results did not showed a significant association with schizophrenia in Asian populations. Our findings suggest that neither common genetic variations of TPH1 nor TPH2 are likely to contribute to the genetic susceptibility to schizophrenia in Japanese population.