Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.