Association of alpha2A-adrenergic receptor gene polymorphism with susceptibility to suicide in Japanese females

OBJECTIVES: It has been suggested that noradrenergic system abnormalities are involved in suicide. Postmortem brain studies have shown that molecular and functional alterations in alpha2A-adrenergic receptor-induced signal transduction are associated with suicide and depression. Recently, a single nucleotide polymorphism (SNP) within a coding region of the alpha2A-adrenergic receptor gene (ADRA2A), which results in an Asn-to-Lys change at amino acid 251 (N251K), has been implicated in susceptibility to suicide in Caucasians. The aim of our study is to determine whether genetic variants of the ADRA2A gene are also associated with suicide in a Japanese population. METHODS: Three SNPs, C-1291G, N251K and rs3750625C/A, and one insertion/deletion polymorphism in the ADRA2A gene were genotyped in 184 completed suicides and 221 control subjects with the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Neither variation of the N251K SNP nor the insertion/deletion polymorphism was found in our Japanese samples. The C-1291G SNP in the promoter region was found to be significantly associated with suicide in females (P=0.043 and 0.013 for genotypic and allelic comparisons, respectively). One of the common haplotypes, CC of C-1291G and rs3750625C/A, was also associated with suicide in females (P=0.015). These associations were also significant in the female violent suicide victims (P=0.009 and 0.009 for allelic and CC haplotypic comparisons, respectively). Although the significance was nominal, it was maintained even after correction for multiple comparisons. By contrast, neither of these two SNPs showed any association with violent and/or non-violent suicide in males. CONCLUSION: Our results raise the possibility that promoter genetic variation in the ADRA2A gene is associated with either suicide or violent suicide in females.