Japanese Cohort Study Identifies an Association Between the Serotonin Transporter–Linked Polymorphic Region and Suicide Death

INTRODUCTION: More than 720 000 individuals die by suicide annually worldwide, making it a major public health concern and a leading cause of death among young people, particularly in Asian populations. Dysregulation of the 5-hydroxytryptamine system has been implicated in suicide risk. The SLC6A4 gene encodes the serotonin transporter, which regulates synaptic 5-hydroxytryptamine levels. Its promoter region contains a 44-base-pair insertion/deletion polymorphism, known as the serotonin-transporter-linked polymorphic region (5-HTTLPR). We examined the association between the 5-HTTLPR polymorphism and suicide death in a Japanese cohort, representing the largest sample from an Asian population to date. METHODS: We included 448 suicide decedents and 361 controls. Genomic DNA was extracted from peripheral blood, and 5-HTTLPR genotypes were determined using PCR. We evaluated genotype- and allele-level associations with suicide. Additionally, we conducted a meta-analysis incorporating previous studies. RESULTS: The distributions of 5-HTTLPR genotypes and alleles differed significantly between suicide decedents and controls (S allele: OR = 1.62, 95% CI = 1.26-2.09, p < 0.001). The associations remained significant in subgroup analyses by sex, age group, and violent methods. Age- and sex-matched analyses yielded consistent results. However, the random-effects meta-analysis did not demonstrate a significant association. CONCLUSION: Our findings indicate a potential association between 5-HTTLPR polymorphisms and suicide death in a Japanese population. Although further research in larger and diverse samples is warranted, these results may contribute to a better understanding of the biological underpinnings of suicide risk.