Polymorphisms in 5-HTR1A and coupled G-proteins in association with negative life events increase susceptibility to suicide attempt

Suicide refers to an individual in a complex psychological state who, under intentional or voluntary action, takes various means to end their life. Importantly, 50%-70% of suicide deaths associated with mental disorders are in patients that suffer from depression. In this study, we investigated whether there were correlations between negative life events and genetic polymorphisms in the 5-HT receptor 1A (HTR1A) and its coupled G-protein gene that contribute to the incidence of suicidal behavior in depression patients. The admission criteria for this study excluded patients with psychotic spectrum disorders and active substance use. Clinical depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Single nucleotide polymorphism (SNP) genotyping was performed by the Taqman allelic discrimination assay among 449 patients with clinical depression (suicide attempts: 98 and non-suicide attempts: 351). The frequency and severity of negative life events were measured using the Life Events Scale. Individual SNP genotype and allele frequencies were compared between the groups by X² test, and gene-environment interactions were analyzed by logistic regression models. There were no significant associations between the four SNPs and suicide attempts in depression patients. Analyses assuming a single contribution of each gene-environment interaction to suicide attempt risk in individuals carrying the C/C genotype of rs5443, the C/C genotype of rs6295 or the C/C genotype of rs878567, in combination with high-negative life events, showed a trend for an interaction between these SNPs and high negative life events impacting the history of suicide attempts among depression patients in the Chinese population. These results suggest that HTR1A and GNB3 variations interact with environmental factors to increase the risk of suicide attempt in depression patients in the Chinese population.