title: Gene expression and association analyses of the phosphodiesterase 4B (PDE4B) gene in major depressive disorder in the Japanese population.
abstract: The phosphodiesterase 4B (PDE4B) interacts with disrupted-in-schizophrenia 1 (DISC1), which is a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). PDE4B is also important in the regulation of cAMP signaling, a second messenger implicated in learning, memory, and mood. In this study, we determined mRNA expression levels of the PDE4B gene in the peripheral blood leukocytes of patients with MDD and control subjects (n = 33, each). Next we performed two-stage case-controlled association analyses (first set; case = 174, controls = 348; second set; case = 481, controls = 812) in the Japanese population to determine if the PDE4B gene is implicated in MDD. In the leukocytes, a significantly higher expression of the PDE4B mRNA was observed in the drug-naïve MDD patients compared with control subjects (P < 0.0001) and the expression of the MDD patients significantly decreased after antidepressant treatment (P = 0.030). In the association analysis, we observed significant allelic associations of four SNPs (the most significant, rs472952; P = 0.002) and a significant haplotypic association (permutation P = 0.019) between the PDE4B gene and MDD in the first-set samples. However, we could not confirm these significant associations in the following independent second-set of samples. Our results suggest that the PDE4B gene itself does not link to MDD but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD.
authors.affiliation: Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. shu-numata@umin.ac.jp
authors.forename: Shusuke
authors.initials: S
authors.lastname: Numata
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Iga
authors.forename: Masahito
authors.initials: M
authors.lastname: Nakataki
authors.forename: Shin'ya
authors.initials: S
authors.lastname: Tayoshi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Satsuki
authors.initials: S
authors.lastname: Sumitani
authors.forename: Masahito
authors.initials: M
authors.lastname: Tomotake
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kamegaya
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tatsumi
authors.forename: Akira
authors.initials: A
authors.lastname: Sano
authors.forename: Takashi
authors.initials: T
authors.lastname: Asada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohmori
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000097:blood / Q000235:genetics*; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4