title: The Gem interacting protein (GMIP) gene is associated with major depressive disorder.
abstract: 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.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tadokoro
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tatsumi
authors.forename: Asako
authors.initials: A
authors.lastname: Kosuga
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Kamijima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000473:pathology; D017931:DNA Primers; D003866:Depressive Disorder / Q000235:genetics* / Q000473:pathology; D020690:GTPase-Activating Proteins / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; C474310:GMIP protein, human; D020690:GTPase-Activating Proteins