Are serotonin 3A and 3B receptor genes associated with suicidal behavior in schizophrenia subjects?

Suicide is a major contributor to the morbidity and mortality of schizophrenia, accounting for approximately 10% of deaths in these patients. Genetic factors have been reported to modulate the risk for suicide, although the precise mechanism and magnitude of the genetic contribution are unknown. Further, suicide attempters present abnormalities in the serotonergic system. We evaluated whether genetic variants in the serotonin receptors HTR3A (rs897692, rs1150226, rs1176724, rs2276302, rs3737457, rs897687 and rs1176713) and HTR3B (rs3758987, rs10502180, rs11606194, rs17116121, rs1176744, rs17116138, rs2276307, rs3782025 and rs1176761) were susceptibility components for suicidal behavior in 154 Caucasians schizophrenia subjects (20.1% of suicide attempters). In a second step, we compared haplotype and gene–gene interaction approaches because both genes are located in the chromosome 11q23 approximately 28 Kbp apart. We did not observe allelic or genotypic associations. Six haplotypes were nominally significant associated with suicide. Gene–gene interaction using Helix Tree software showed two nominally significant interactions reproduced by haplotype association. Likewise, haplotypes composed by the markers included in the best multidimensional reduction three-locus model were nominally significant. Our results suggest that HTR3A and HTR3B polymorphisms may not play a major role in the susceptibility for suicidal behavior in schizophrenia subjects. Moreover, gene–gene interaction and haplotype association may have consistent results for genes located in the same chromosome.

Research highlights▶ Genetic variants of HTR3A and HTR3B are not associated with suicide attempt in schizophrenia. ▶ Haplotype and gene–gene interaction analysis may have consistent results for gene located on the same chromosome when gene–gene interaction results are robust. ▶ Different gene–gene interaction methods may lead to different results.