title: Gene×gene×gender interaction of BDNF and COMT genotypes associated with panic disorder.
abstract: Genetic and gender differences are among the factors that have a role in the etiology of panic disorder (PD). It is thought that PD is related to neurotransmitter pathways, such as brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT), both of which are involved in the regulation of the monoamine mechanism. We examined the interactions of BDNF, COMT and gender differences in terms of personality characteristics in PD. The subjects were 470 patients (178 men, 292 women) with a DSM-IV diagnosis of PD, and 458 healthy controls (195 men, 263 women). The subjects were further clinically characterized using the Revised NEO Personality Inventory (NEO-PI-R) and State-Trait Anxiety Inventory (STAI). COMT Val158Met polymorphisms (rs4680) and BDNF Val66Met (rs6265) polymorphisms were genotyped using allelic discrimination by a real-time PCR assay. A multivariate analysis of covariance (MANCOVA) was performed with STAI and NEO-PI-R scores as the dependent factor, gender and genotyping groups (BDNF and COMT) as fixed factors, and the covariate of age in the PD and healthy control groups. Post hoc MANCOVA tests were conducted to evaluate COMT × BDNF interactions. An interaction of BDNF × COMT × gender was confirmed in the PD group by MANCOVA on STAI scores and NEO-PI-R Neuroticism and Extraversion scores, whereas no association of such interactions was observed in the healthy controls. The anxiety sensitivity of the COMT Met+BDNF Val/Val carriers was higher than that of the COMT Val/Val+BDNF Val/Val carriers by post hoc MANCOVA. A significant BDNF × COMT × gender interaction was observed in the PD patients but not in the controls. Our findings partly demonstrated the involvement of a gene × gene × gender interaction in the pathogenesis of PD.
authors: Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center (BSAM), Mie University, Mie, Japan.
authors: Yoshiaki
authors: Y
authors: Konishi
authors: Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center (BSAM), Mie University, Mie, Japan. Electronic address: h-tanii@clin.medic.mie-u.ac.jp.
authors: Hisashi
authors: H
authors: Tanii
authors: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Otowa
authors: Laboratory of Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan.
authors: Tsukasa
authors: T
authors: Sasaki
authors: Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan.
authors: Mamoru
authors: M
authors: Tochigi
authors: Division for Environment, Health and Safety, The University of Tokyo, Tokyo, Japan.
authors: Tadashi
authors: T
authors: Umekage
authors: Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center (BSAM), Mie University, Mie, Japan.
authors: Eishi
authors: E
authors: Motomura
authors: Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center (BSAM), Mie University, Mie, Japan.
authors: Takashi
authors: T
authors: Shiroyama
authors: Research Center for Panic Disorder, Nagoya Mental Clinic, Aichi, Japan.
authors: Hisanobu
authors: H
authors: Kaiya
authors: Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.
authors: Yuji
authors: Y
authors: Okazaki
authors: Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Brain Science and Animal Model Research Center (BSAM), Mie University, Mie, Japan.
authors: Motohiro
authors: M
authors: Okada
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000235:genetics*; D010555:Personality Inventory; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011581:Psychological Tests; D012727:Sex Characteristics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: BDNF; COMT; Gender; Gene×gene×gender interaction; Panic disorder