TPH2 is not a susceptibility gene for suicide in Japanese population

Serotonergic systems mediate a control of aggression and/or impulsivity in human and are suggested to be involved in suicidal behavior. The newly identified neuronal tryptophan hydroxylase isoform 2 (TPH2), the rate-limiting enzyme in serotonin synthesis, represents a prime candidate in numerous genetic association analyses of suicidal behavior; however, the results are still inconclusive. The discrepancy may result from the heterogeneity of pathogenesis of suicidal behavior and/or methodological mismatches. We, therefore, attempted to replicate the association of TPH2 gene with suicide using a case-control study of 234 completed suicides and 260 control subjects in Japanese population.

We genotyped 15 tagging-single nucleotide polymorphisms (SNPs) including 4 SNPs, which were previously reported to be associated with suicidal behavior, using the TaqMan probe assays and the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.

We found no significant differences in genotypic distributions (uncorrected p=0.06-0.98) or allelic frequencies (uncorrected p=0.09-0.95) of the fifteen SNPs between the completed suicides and control groups. Haplotypes constructed with these SNPs were also not associated with suicide (uncorrected p=0.03-0.96 and corrected p=0.20-1.00). Even when we took sex and suicidal methods (violent or non-violent) into account for the analyses, no significant differences in genotypic distributions, allelic/haplotypic frequencies were found in the two groups.

Our results suggest that the common SNPs and haplotypes of the TPH2 gene are unlikely to contribute to the genetic susceptibility to suicidal behavior in Japanese population.