The Gem interacting protein (GMIP) gene is associated with major depressive disorder

Major depressive disorder (MDD) is a mood disorder with a significant heritable component. Structural neuronal impairment has been considered to be implicated in MDD, as it leads to brain morphological alterations such as hippocampal atrophy. The Gem interacting protein, GMIP, is a novel Rho GTPase-activating protein known to play important roles in neurite growth and axonal guidance. We examined the GMIP gene for possible association in a Japanese sample of 164 patients with MDD and 164 controls matched for sex. We found a significant association with MDD for one single nucleotide polymorphism (SNP) (-525G/A) located on the 5'-upstream region of the GMIP gene (p=0.039, odds ratio 1.66, 95% CI 1.05-2.69) and stronger evidence for association in a multimarker haplotype analysis (p=0.004). We then performed a promoter-luciferase reporter assay; the promoter activity for -525A allele, which was in excess in the MDD patients, was significantly decreased compared with the -525G allele in transient transfection experiments using three types of cell lines. Our results suggest that genetic variations in the GMIP gene can confer susceptibility to MDD, and the associated promoter SNP might play a role in the transcriptional regulation of the GMIP gene. Further study needs to be undertaken to validate the association between the GMIP gene and MDD.